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Calcium ions play a key role in the physiological processes of the central nervous system. The intracellular calcium signal, in nerve cells, is part of the neurotransmission mechanism. They are responsible for stabilizing membrane potential and controlling the excitability of neurons. Calcium ions are a universal second messenger that participates in depolarizing signal transduction and contributes to synaptic activity. These ions take an active part in the mechanisms related to memory and learning. As a result of depolarization of the plasma membrane or stimulation of receptors, there is an extracellular influx of calcium ions into the cytosol or mobilization of these cations inside the cell, which increases the concentration of these ions in neurons. The influx of calcium ions into neurons occurs via plasma membrane receptors and voltage-dependent ion channels. Calcium channels play a key role in the functioning of the nervous system, regulating, among others, neuronal depolarization and neurotransmitter release. Channelopathies are groups of diseases resulting from mutations in genes encoding ion channel subunits, observed including the pathophysiology of neurological diseases such as migraine. A disturbed ability of neurons to maintain an appropriate level of calcium ions is also observed in such neurodegenerative processes as Alzheimer's disease, Parkinson's disease, Huntington's disease, and epilepsy. This review focuses on the involvement of calcium ions in physiological and pathological processes of the central nervous system. We also consider the use of calcium ions as a target for pharmacotherapy in the future. [ABSTRACT FROM AUTHOR]

Neurological disorders are the primary cause of human disability and mortality globally, however, current medications slightly alleviate some symptoms of degenerative diseases. Serine is an important amino acid for the brain function and involved in a variety of biosynthetic pathways and signal transduction processes. The imbalance of serine metabolism is associated with neurodegeneration, including neuroinflammation, oxidative stress and apoptosis. Altered activities of serine metabolizing enzymes and accumulation of serine metabolites affect the survival and function of nerve cells. Abnormal serine levels are observed in animal models with neurological diseases, but not all human studies, therefore, the maintenance of serine homeostasis is a potentially therapeutic strategy for neurological disorders. To date, physiological and pharmacological roles of serine in neurological diseases have not been systemically recapitulated, and the association between serine and neurological diseases is controversial. In this review, we summarize physicochemical properties of serine, biological processes of serine in the brain (source, biotransformation, and transport), and the application of serine in neurological diseases including Alzheimer's disease, schizophrenia, and depression. Here, we highlight physicochemistry, physiology, pharmacology, and therapeutic potentials of serine in the prevention and treatment of neurological dysfunction. Our work provides valuable hints for future investigation that will lead to a comprehensive understanding of serine and its metabolism in cellular physiology and pharmacology. Although broad by necessity, the review helps researchers to understand great potentials of serine in the prevention and treatment of neurological dysfunction. [ABSTRACT FROM AUTHOR]

Amentoflavone (AME) is a flavonoid compound found in over 120 plants. Its extensive pharmacological activity for treating cardiocerebrovascular diseases and neurological disorders have attracted the attention of researchers in recent years. However, owing to the poor solubility and low bioavailability of AME, it has not been developed as a drug for treating these diseases. This review focuses on two aspects of AME: First, it provides a detailed summary and introduction to AME based on its chemical structure, physicochemical properties, plant sources, extraction and purification methods, administration systems, and pharmacokinetic properties. Second, it summarizes the effects of AME on cardiocerebrovascular diseases and neurological disorders, and its specific pharmacological mechanisms. This review aims to promote the use of AME for treating cardiocerebrovascular diseases and neurological disorders. AME exhibits multiple activities, indicating its potential as a natural drug for treating these diseases. Further studies on its pharmacokinetics and toxicology are required to ensure its safety and efficacy. [ABSTRACT FROM AUTHOR]

In neuroscience research, chiral metabolomics is an emerging field, in which D-amino acids play an important role as potential biomarkers for neurological diseases. The targeted chiral analysis of the brain metabolome, employing liquid chromatography (LC) coupled to mass spectrometry (MS), is a pivotal approach for the identification of biomarkers for neurological diseases. This review provides an overview of D-amino acids in neurological diseases and of the state-of-the-art strategies for the enantioselective analysis of chiral amino acids (AAs) in biological samples to investigate their putative role as biomarkers for neurological diseases. Fluctuations in D-amino acids (D-AAs) levels can be related to the pathology of neurological diseases, for example, through their role in the modulation of N-methyl-D-aspartate receptors and neurotransmission. Because of the trace presence of these biomolecules in mammals and the complex nature of biological matrices, highly sensitive and selective analytical methods are essential. Derivatization strategies with chiral reagents are highlighted as critical tools for enhancing detection capabilities. The latest advances in chiral derivatization reactions, coupled to LC-MS/MS analysis, have improved the enantioselective quantification of these AAs and allow the separation of several chiral metabolites in a single analytical run. The enhanced performances of these methods can provide an accurate correlation between specific D-AA profiles and disease states, allowing for a better understanding of neurological diseases and drug effects on the brain. [ABSTRACT FROM AUTHOR]

Peroxisomes and pexophagy have gained increasing attention in their role within the central nervous system (CNS) in recent years. In this review, we comprehensively discussed the physiological and pathological mechanisms of peroxisomes and pexophagy in neurological diseases. Peroxisomes communicate with mitochondria, endoplasmic reticulum, and lipid bodies. Their types, sizes, and shapes vary in different regions of the brain. Moreover, peroxisomes play an important role in oxidative homeostasis, lipid synthesis, and degradation in the CNS, whereas its dysfunction causes various neurological diseases. Therefore, selective removal of dysfunctional or superfluous peroxisomes (pexophagy) provides neuroprotective effects, which indicate a promising therapeutic target. However, pexophagy largely remains unexplored in neurological disorders. More studies are needed to explore the pexophagy's crosstalk mechanisms in neurological pathology. [ABSTRACT FROM AUTHOR]

Background: Commercial genome‐wide genotyping arrays have historically neglected coverage of genetic variation across populations. Objective: We aimed to create a multi‐ancestry genome‐wide array that would include a wide range of neuro‐specific genetic content to facilitate genetic research in neurological disorders across multiple ancestral groups, fostering diversity and inclusivity in research studies. Methods: We developed the Illumina NeuroBooster Array (NBA), a custom high‐throughput and cost‐effective platform on a backbone of 1,914,934 variants from the Infinium Global Diversity Array and added custom content comprising 95,273 variants associated with more than 70 neurological conditions or traits, and we further tested its performance on more than 2000 patient samples. This novel platform includes approximately 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease–related genome‐wide association study loci across diverse populations. Results: In this article, we describe NBA's potential as an efficient means for researchers to assess known and novel disease genetic associations in a multi‐ancestry framework. The NBA can identify rare genetic variants and accurately impute more than 15 million common variants across populations. Apart from enabling sample prioritization for further whole‐genome sequencing studies, we envisage that NBA will play a pivotal role in recruitment for interventional studies in the precision medicine space. Conclusions: From a broader perspective, the NBA serves as a promising means to foster collaborative research endeavors in the field of neurological disorders worldwide. Ultimately, this carefully designed tool is poised to make a substantial contribution to uncovering the genetic etiology underlying these debilitating conditions. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]

Canine visceral leishmaniasis (CVL) is a parasitic disease caused by the protozoan Leishmania infantum. Neurological infection occurs due to the parasite's ability to cross the blood–brain barrier. It is known that dogs can remain infected with a subclinical infection for life, potentially acting as reservoirs for L. infantum when bitten by sandflies. In this context, the objective of this study was to evaluate the occurrence of Leishmania spp. in the brains of dogs from the metropolitan region of Rio Grande do Sul, Brazil, without a history of neurological disease but residing in an endemic area for L. infantum. A total of 200 samples, from 2022 to 2023, were evaluated using conventional Polymerase Chain Reaction (PCR) with the primers Leishmini-F GGKAGGGGCGTTCTGC and Leishmini-R STATWTTACACCAACCCC, aiming to amplify a product of 120 base pairs for Leishmania spp. To identify the species, a multiplex PCR was used, differentiating L. braziliensis (127 bp), L. amazonensis (100 bp), and L. infantum (60 bp), with the molecular target being the conserved region of the kinetoplast DNA (kDNA) minicircle, specific to Leishmania spp. Of the 200 samples evaluated, 26.5% (53/200) tested positive in the conventional PCR reaction for Leishmania spp., with the PCR multiplex the only species detected was Leishmania infantum. The average age of the positive animals was 5.08 years, with 47.2% being females and 52.8% being males; among these, mixed-breed dogs were the most predominant, representing 43.4% of the total. Clinical signs varied: hepatomegaly in two dogs, pronounced neutrophilic hepatitis in one, splenomegaly in one with lymphoid hyperplasia, and glomerulonephritis and nephritis in two animals. Mild anemia and thrombocytopenia were found in eight, with pale mucous membranes in three, and diffuse alveolar edema in one case. Notable pathological findings included suspected distemper in one animal and lymphoplasmacytic meningitis in another. Histopathological findings revealed alveolar edema and acute renal failure. A third dog exhibited bilateral hydrocephalus and diffuse edema in the brain. Additional changes, such as mild inflammatory infiltrate and slight vacuolar degeneration, were observed in 11.3% of the analyzed brains. There was no clinical suspicion of leishmaniasis in any of the studied cases. Therefore, the detection of L. infantum DNA in the brains of dogs suggests that animals with subclinical infection may play a crucial role in the spread of leishmaniasis, and infection by Leishmania spp. should be considered as a differential diagnosis for neurological disease in endemic areas for the protozoan. [ABSTRACT FROM AUTHOR]

Neurological diseases are a major cause of the global burden of disease. Although the mechanisms of the occurrence and development of neurological diseases are not fully clear, most of them are associated with cells mediating neuroinflammation. Yet medications and other therapeutic options to improve treatment are still very limited. Single-cell RNA sequencing (scRNA-seq), as a delightfully potent breakthrough technology, not only identifies various cell types and response states but also uncovers cell-specific gene expression changes, gene regulatory networks, intercellular communication, and cellular movement trajectories, among others, in different cell types. In this review, we describe the technology of scRNA-seq in detail and discuss and summarize the application of scRNA-seq in exploring neurological diseases, elaborating the corresponding specific mechanisms of the diseases as well as providing a reliable basis for new therapeutic approaches. Finally, we affirm that scRNA-seq promotes the development of the neuroscience field and enables us to have a deeper cellular understanding of neurological diseases in the future, which provides strong support for the treatment of neurological diseases and the improvement of patients' prognosis. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion High positivity rate of skin phosphorylated α‐synuclein (P‐SYN) was observed in Parkinson's disease (PD). Bullous pemphigoid (BP) is one of the most common autoimmune skin diseases associated with PD.Our aim was to investigate whether BP patients might be a targeted risk population for the screening of skin P‐SYN.Skin P‐SYN expression was evaluated by immunohistochemistry in BP patients with/without PD.Twenty‐two BP patients with PD, 24 BP patients without PD, and seven healthy donors were enrolled. Colocalization of P‐SYN and PGP9.5 was found in all BP patients, but only one healthy control, whereas BP patients with PD showed higher expression than BP patients without PD (mean ± standard deviation, 10.7 ± 6.7 vs. 7.3 ± 3.2; P = 0.027). Positive expression was mainly observed in basement membrane zone and dermis.These results indicated BP patients might be a targeted risk population for the screening of skin P‐SYN, which was helpful for the detection of PD early. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Methylation, a key epigenetic modification, is essential for regulating gene expression and protein function without altering the DNA sequence, contributing to various biological processes, including gene transcription, embryonic development, and cellular functions. Methylation encompasses DNA methylation, RNA methylation and histone modification. Recent research indicates that DNA methylation is vital for establishing and maintaining normal brain functions by modulating the high-order structure of DNA. Alterations in the patterns of DNA methylation can exert significant impacts on both gene expression and cellular function, playing a role in the development of numerous diseases, such as neurological disorders, cardiovascular diseases as well as cancer. Our current understanding of the etiology of neurological diseases emphasizes a multifaceted process that includes neurodegenerative, neuroinflammatory, and neurovascular events. Epigenetic modifications, especially DNA methylation, are fundamental in the control of gene expression and are critical in the onset and progression of neurological disorders. Furthermore, we comprehensively overview the role and mechanism of DNA methylation in in various biological processes and gene regulation in neurological diseases. Understanding the mechanisms and dynamics of DNA methylation in neural development can provide valuable insights into human biology and potentially lead to novel therapies for various neurological diseases. [ABSTRACT FROM AUTHOR]

Neurons are interactive cells that connect via ions to develop electromagnetic fields in the brain. This structure functions directly in the brain. Connectome is the data obtained from neuronal connections. Since neural circuits change in the brain in various diseases, studying connectome sheds light on the clinical changes in special diseases. The ability to explore this data and its relation to the disorders leads us to find new therapeutic methods. Artificial intelligence (AI) is a collection of powerful algorithms used for finding the relationship between input data and the outcome. AI is used for extraction of valuable features from connectome data and in turn uses them for development of prognostic and diagnostic models in neurological diseases. Studying the changes of brain circuits in neurodegenerative diseases and behavioral disorders makes it possible to provide early diagnosis and development of efficient treatment strategies. Considering the difficulties in studying brain diseases, the use of connectome data is one of the beneficial methods for improvement of knowledge of this organ. In the present study, we provide a systematic review on the studies published using connectome data and AI for studying various diseases and we focus on the strength and weaknesses of studies aiming to provide a viewpoint for the future studies. Throughout, AI is very useful for development of diagnostic and prognostic tools using neuroimaging data, while bias in data collection and decay in addition to using small datasets restricts applications of AI-based tools using connectome data which should be covered in the future studies. [ABSTRACT FROM AUTHOR]

Neurological disorders are being increasingly recognized as major causes of death and disability around the world. Neurological disorders refer to a broad range of medical conditions that affect the brain and spinal cord. These disorders can have various causes, including genetic factors, infections, trauma, autoimmune reactions, or neurodegenerative processes. Each disorder has its own unique symptoms, progression, and treatment options. Optimal communication between interneurons and neuron-glia cells within the homeostatic microenvironment is of paramount importance. Within this microenvironment, exosomes play a significant role in promoting intercellular communication by transferring a diverse cargo of contents, including proteins, lipids, and non-coding RNAs (ncRNAs). Partially, nervous system homeostasis is preserved by various stem cell-derived exosomal ncRNAs, which include circular RNAs (circRNAs), long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and PIWI-interacting RNAs (piRNAs). The diversity of these exosomal ncRNAs suggests their potential to influence multiple pathways and cellular processes within the nervous system. Stem cell-derived exosomes and their ncRNA contents have been investigated for potential therapeutic uses in neurological disorders, owing to their demonstrated capabilities in neuroprotection, neuroregeneration, and modulation of disease-related pathways. The ability of stem cell-derived exosomes to cross the blood-brain barrier makes them a promising delivery vehicle for therapeutic ncRNAs. This review aims to summarize the current understanding of different stem cell-derived exosomal ncRNAs and their therapeutic potential and clinical applications. [ABSTRACT FROM AUTHOR]

Background: The causal relationship between cathepsins and neurological diseases remains uncertain. To address this, we utilized a two-sample Mendelian randomization (MR) approach to assess the potential causal effect of cathepsins on the development of neurological diseases. Methods: This study conducted a two-sample two-way MR study using pooled data from published genome-wide association studies to evaluate the relationship between 10 cathepsins (B, D, E, F, G, H, L2, O, S, and Z) and 7 neurological diseases, which included ischemic stroke, cerebral hemorrhage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and epilepsy. The analysis employed various methods such as inverse variance weighting (IVW), weighted median, MR Egger regression, MR pleiotropy residual sum and outlier, Cochran Q statistic, and leave-one-out analysis. Results: We found a causal relationship between cathepsins and neurological diseases, including Cathepsin B and Parkinson's disease (IVW odds ratio (OR): 0.89, 95% confidence interval (CI): 0.83, 0.95, p = 0.001); Cathepsin D and Parkinson's disease (OR: 0.80, 95%CI: 0.68, 0.95, p = 0.012); Cathepsin E and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.09, p = 0.015); Cathepsin O and ischemic stroke (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.021). Reverse MR analyses revealed that multiple sclerosis and Cathepsin E (OR: 1.05, 95%CI: 1.01, 1.10, p = 0.030). There is currently no significant relationship has been found between other cathepsins and neurological diseases. Conclusion: Our study reveals a causal relationship between Cathepsins B, D, E, and O and neurological diseases, offering valuable insights for research aimed at improving the diagnosis and treatment of such conditions. [ABSTRACT FROM AUTHOR]

Astrocytes are essential for maintaining brain homeostasis. Alterations in their activity have been associated with various brain pathologies. Sex differences were reported to affect astrocyte development and activity, and even susceptibility to different neurodegenerative diseases. This review aims to summarize the current knowledge on the effects of sex on astrocyte activity in health and disease. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods: We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results: The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions: Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals. [ABSTRACT FROM AUTHOR]

Autophagy, a lysosome-dependent protein degradation mechanism, is a highly conserved catabolic process seen in all eukaryotes. This cell protection system, which is present in all tissues and functions at a basic level, can be up- or downregulated in response to various stresses. A disruption in the natural route of the autophagy process is frequently followed by an interruption in the inherent operation of the body’s cells and organs. Probiotics are live bacteria that protect the host through various mechanisms. One of the processes through which probiotics exert their beneficial effects on various cells and tissues is autophagy. Autophagy can assist in maintaining host homeostasis by stimulating the immune system and affecting numerous physiological and pathological responses. In this review, we particularly focus on autophagy impairments occurring in several human illnesses and investigate how probiotics affect the autophagy process under various circumstances.Abbreviation: AD: Alzheimer disease; AKT: AKT serine/threonine kinase; AMPK: 5′AMP-activated protein kinase; ATG: autophagy related; CCl4: carbon tetrachloride; CFS: cell-free supernatant; CMA: chaperone-mediated autophagy; CRC: colorectal cancer; EPS: L. plantarum H31 exopolysaccharide; HD: Huntington disease; HFD: high-fat diet; HPV: human papillomavirus; IFNG/IFN-γ: interferon gamma; IL6: interleukin 6; LGG: L. rhamnosus GG; LPS: lipopolysaccharide; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PD: Parkinson disease; Pg3G: pelargonidin-3-O-glucoside; PI3K: phosphoinositide 3-kinase; PolyQ: polyglutamine; ROS: reactive oxygen species; SCFAs: short-chain fatty acids; SLAB51: a novel formulation of lactic acid bacteria and bifidobacteria; Slp: surface layer protein (of acidophilus NCFM); SNCA: synuclein alpha; ULK1: unc-51 like autophagy-activating kinase 1; YB: B. longum subsp. infantis YB0411; YFP: yeast fermentate prebiotic. [ABSTRACT FROM AUTHOR]

Neurological diseases represent a spectrum of complex disorders characterized by degradation of nerve cells or nerve tissue within the nervous system. Currently, optimal therapeutic interventions for neurological diseases as a significant threat to human health are lacking. Electrospinning, as a widely used nanotechnology methos, is capable of producing a wide range of micro- and nano-structures with the excellent structure, high specific surface area, and superior drug loading capacity. It also provides the solution properties including viscosity, elasticity, conductivity, and surface tension. The improvements of electrospinning devices can be achieved by controlling variables including voltage, zeta potential, distance between electrospinning nozzle and the collector, and also, environmental parameters including temperature and humidity. Hence, electrospinning could mimic the complex neural tissue structure, regulate the behavior of neuronal cells, and even deliver the drugs across the blood-brain barrier, showing excellent application prospects in neurological diseases. In this review, we summarize the recent improvements of electrospinning and the recent applications of electrospinning in neurological diseases, hoping that it may provide the valuable insights for researchers in the field of nanomaterials. [ABSTRACT FROM AUTHOR]

Nanomedicine, leveraging the unique properties of nanoparticles, has revolutionized the diagnosis and treatment of neurological diseases. Among various nanotechnological advancements, ultrasound-mediated drug delivery using micro- and nanobubbles offers promising solutions to overcome the blood-brain barrier (BBB), enhancing the precision and efficacy of therapeutic interventions. This review explores the principles, current clinical applications, challenges, and future directions of ultrasound-mediated drug delivery systems in treating stroke, brain tumors, neurodegenerative diseases, and neuroinflammatory disorders. Additionally, ongoing clinical trials and potential advancements in this field are discussed, providing a comprehensive overview of the impact of nanomedicine on neurological diseases. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a complex immune‐mediated disease with no currently known cure. There is growing evidence to support the role of diet in reducing some of the symptoms and disease progression in MS, and we previously developed and tested the feasibility of a digital nutrition education program for people with MS. Objective: The aim of this study was to explore factors that influenced engagement in the digital nutrition education program, including features influencing capability, opportunity and motivation to change their dietary behaviours. Methods: Semi‐structured interviews were conducted with people who had MS, and who completed some or all of the program until data saturation was reached. Interviews were analysed inductively using thematic analysis. Themes were deductively mapped against the COM‐B (Capability, Opportunity, Motivation, Behaviour) behaviour change model. Results: Sixteen interviews were conducted with participants who completed all (n = 10) or some of the program (n = 6). Four themes emerged: (1) acquiring and validating nutrition knowledge; (2) influence of time and social support; (3) getting in early to improve health and (4) accounting for food literacy experiences. Discussion: This is the first online nutrition program with suitable behavioural supports for people with MS. It highlights the importance of disease‐specific and evidence‐based nutrition education to support people with MS to make dietary changes. Acquiring nutrition knowledge, coupled with practical support mechanisms, such as recipe booklets and goal setting, emerged as crucial for facilitating engagement with the program. Conclusions: When designing education programs for people with MS and other neurological conditions, healthcare professionals and program designers should consider flexible delivery and building peer support to address the needs and challenges faced by participants. Patient or Public Contribution: Members of the MS Nutrition Research Program Stakeholder Reference Group, which includes people with MS and MS health professionals, provided input during the development of the nutrition education program and study design stages. [ABSTRACT FROM AUTHOR]

Background: Patients with non-cancer disease are less likely to receive specialized palliative care than cancer patients. To be able to provide the best specialized palliative care, it is important to understand palliative care needs of non-cancer patients and whether the type and level of needs differ from those of cancer patients. Large studies including both cancer and non-cancer patients, using validated needs-assessment-tools, are needed to understand differences in palliative care needs at admittance to specialized palliative care. Aims: To compare palliative care needs at the start of palliative care for cancer and non-cancer disease. Design: Six-year nationwide register-based study. Setting/participants: This study included patients from all Danish specialized palliative care services (hospice care, hospital-based palliative care, home-based palliative care, or consultation) who completed a need-assessment-questionnaire. Ordinal logistic regression was performed to study the association between diagnosis and needs. Results: Cancer patients had a higher probability of receiving specialized palliative care. Of the 44,315 palliative care admissions included in this study, 93.3% were on cancer patients. Independent of diagnosis patients experienced on average six needs and high levels of fatigue and impaired physical functioning. Non-cancer patients had significantly higher odds of insomnia, fatigue and impaired emotional functioning, physical functioning, and quality of life whereas cancer patients had higher odds of pain (except for patients with neurological disease). Conclusions: The higher levels of several symptoms/problems among non-cancer patients compared to cancer patients suggests that referral to specialized palliative care should be improved for non-cancer patients perhaps by improving identification of palliative needs. [ABSTRACT FROM AUTHOR]

The interplay between mitochondria, epigenetics, and the microbiota is intricately linked to both health and disease. Within our cells, a complex molecular dance occurs, where these components intertwine in a mesmerizing ballet that plays a decisive role in our health. Mitochondria, beyond being energy powerhouses, modulate nuclear gene expression through messengers like reactive oxidative stress (ROS) and calcium. Epigenetics, acting as the molecular conductor, regulates the expression of both nuclear and mitochondrial genes through modifications like DNA methylation. The intestinal microbiota itself produces short-chain fatty acids (SCFAs) that influence mitochondrial activity. SCFA-induced epigenetic modifications, like histone acetylation, impact mitochondrial function which may lead to disease. Mitochondrial dysfunction generates retrograde signals that alter nuclear gene expression, as evidenced by increased histone H3 lysine 27 acetylation (H3K27ac) in genes essential for neuronal differentiation and mitochondrial reprogramming. Alterations in the mitochondrial-nuclear-microbiota axis are associated with diseases including diabetes, neurodegeneration, and cancer. Modulating the intestinal microbiota with probiotics or prebiotics can restore balance while intervening in mitochondrial pathways, which can be a therapeutic strategy. Additionally, using epigenetic agents like histone deacetylase (HDAC) inhibitors can reprogram gene expression and improve mitochondrial function. Finally, the present review aims to explore the central interplay between mitochondria, epigenetics modifications, and microbiota in a complex and dynamic molecular context that plays a fundamental role in human health. Specifically, it will examine the impact of microbiome components and metabolites generated from normobiosis and dysbiosis on mitochondria and epigenetic modifications across different diseases and metabolic conditions. This integrated understanding of the molecular players and their interactions provides a deeper perspective on how to promote health and potentially combat disease. [ABSTRACT FROM AUTHOR]

Background and Objectives: Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting mainly elderly patients. Still, little is known about the pathogenesis of pruritus in BP or the factors that affect the clinical course of the disease. This study aimed to evaluate the factors influencing the clinical course of BP among older patients. Materials and Methods: A retrospective analysis of medical records of 55 patients with BP hospitalized in the dermatology department in 2015–2021 was conducted. The study focused on preliminary diagnosis, medical history, clinical examination (characteristics and location of cutaneous changes), laboratory investigation, and direct and indirect immunofluorescence. Results: Analysis of laboratory results in combination with the clinical course of BP showed that red blood cell count, hemoglobin, and hematocrit values were negatively associated with a risk of erosions and erythema, while MCHC values were positively correlated with a risk of associated pruritus. A correlation was found between neurological diseases and an increased risk of erosions. Conclusions: We have shown that age and neurological conditions, including stroke, affect the clinical course of BP. Further studies on a larger group of patients should be conducted to investigate the different factors affecting the clinical aspect of BP and to understand the relationship between them. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To identify what impacts the ketogenic diet (KD) may have on the outcomes of the highly prevalent neurological diseases (NDs) in the UK. These NDs are migraine, traumatic brain injury (TBI), stroke, fibromyalgia and restless legs syndrome (RLS). Additionally, if KD does impact the NDs outcomes, to identify by what biochemical mechanisms that does occur. Methods: Studies using KD as an intervention to treat NDs were identified through electronic database searches which comprise of 4 main themes (highly prevalent NDs, KD, neurological outcomes and biochemical mechanisms). Quality appraisal tools and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used to assess the quality of studies and evidence identified. Results: Twelve articles were identified and no studies for fibromyalgia and RLS. KD had positive impacts on all outcomes in migraine (attack frequency, duration, intensity, etc.) and stroke (balance & coordination, sensation, etc.). KD also had positive impacts on all outcomes in TBI ranging from physical, mental & behaviour and cognitive aspects, except no impact on “anxiety-like behaviour” and “brain oedema”. Improvement of mitochondria metabolism and reduction of neuroinflammation are the common biochemical mechanisms of KD improving the NDs outcomes. The specific mechanisms for migraine, TBI and stroke include inhibition of neuronal excitability, preservation of brain volume and increase in adenosine activity respectively. Conclusion: KD improved almost all outcomes in migraine, TBI and stroke by different biochemical mechanisms. However, cautions are needed to be taken while interpreting the results as RCTs on humans were lacking in this review.

The emerging field of precision medicine relies on scientific breakthroughs to understand disease mechanisms and develop cutting-edge technologies to overcome underlying genetic and functional aberrations. The establishment of the Centre of Excellence for the Technologies of Gene and Cell Therapy (CTGCT) at the National Institute of Chemistry (NIC) in Ljubljana represents a significant step forward, as it is the first centre of its kind in Slovenia. The CTGCT is poised to spearhead advances in cancer immunotherapy and personalised therapies for neurological and other rare genetic diseases. The centre’s overarching mission is to extend beyond the NIC’s scientific excellence in basic research and bring new therapeutic solutions toward clinical application. The CTGCT aims to develop a broad pipeline of biomedical tools, including innovative synthetic biology tools, gene editing and splicing technologies, RNA-based technologies, immune regulation engineering and novel viral and non-viral delivery systems. The CTGCT is supported by partner institutions from the UK, the Netherlands and Germany, which already have academic good manufacturing practice (GMP) facilities for the manufacture of advanced therapy medicinal products (ATMPs) and is committed to active collaboration with clinicians and patient organizations at all stages of development to improve access to gene and cell therapies (GCTs) for patients. The Centre also seeks to collaborate with national and international academic and industrial partners, and the newly established GMP facilities will address a critical bottleneck in the translation of GCTs from research to practice. Finally, CTGCT's translational research and technology transfer units will ensure the impactful dissemination of research and innovation activities in Slovenia, throughout the Western Balkans and Eastern Europe region, and beyond. With its comprehensive approach and forward-looking vision, the CTGCT will drive transformative advances in gene and cell therapies for the benefit of patients on a global scale.

The Functional Independence Measure (FIM) scale is used to assess an individual’s functional capacity. It covers a wide variety of areas of daily life: self-care, sphincter control, transfers, locomotion, communication and social cognition. This tool plays an important role in the professional and academic work of nurses. Therefore, the aim of this paper is to characterize the FIM scale and its use in the care of neurological patients. The FIM scale has been shown to be an accurate and reliable tool for assessing activities of daily living. The FIM consists of 18 items assessing 6 areas of function. The items fall into two domains: motor (13 items) and cognitive (5 items). The respondent can receive from 1 (total assistance — the respondent performs less than 25% of the activity independently) to 7 points (full independence — the analyzed activity is performed safely and quickly) for each activity to be assessed. Many researchers also use the FIM as one of their measurement tools when designing and conducting research. (JNNN 2024;13(3):119–123)

BACKGROUND AND AIMS: Neuroprotection plays an important role in the treatment of brain disorders. In recent years, studies using rat models and clinical trials have demonstrated the positive effects of hydrogen treatment on neurological disorders and brain injuries. Hence, it is of great significance to shed light on this issue. In this article, CiteSpace is employed for visualization and bibliometric analysis of the research frontiers and evolving trends related to the neuroprotective effect of hydrogen. METHODS: All articles published from 2009 to 2023 that discussed the neuroprotective effects of hydrogen in cerebrovascular diseases were retrieved from the Web of Science. Using CiteSpace, a visualization analysis was conducted on aspects such as countries, institutions, authors, keywords, and Co cited references, which enables an intuitive observation of current research hotspots. RESULTS: After manual screening, a total of 106 articles were retrieved. Over time, The number of publications has increased annually. Regarding national contributions, the top three countries with the highest number of publications include China, the United States, and Japan. The Second Military Medical University is the institution that publishes the most articles and has significant influence in the field of hydrogen neuroprotection. Sun, Xuejun and Domoki, Ferenc were the most productive. The most common keywords include hydrogen, oxidative stress, inflammation, and apoptosis. Potential areas of focus for future research consist of early brain injury, hydrogen, ischemia-reperfusion injury and hypothermia treatment. CONCLUSION: The bibliometric study presented herein offers insights into the current status and trends of research on hydrogen in the field of cerebrovascular diseases. Future research trends suggest that hydrogen contributes significantly to the cerebrovascular domain through its anti-inflammatory, antioxidative, and anti-apoptotic mechanisms. This study can aid researchers in identifying hot topics and exploring new research directions.

Abstract Background The growing diffusion of artificial intelligence, data science and digital health has highlighted the role of collection of data and biological samples, thus raising legal and ethical concerns regarding its use and dissemination. Further, the expansion of biobanking, from the basic collection of frozen specimens to the virtual biobanks of specimens and associated data that exist today, has given a revolutionary potential on healthcare systems, particularly in the field of neurological diseases, due to the inaccessibility of central nervous system and the need of non-invasive investigation approaches. Informed Consent (IC) is considered mandatory in all research studies and specimen collections, and must specifically take into account the ethical respect to the individuals to whom the used biological material and data belong. Methods We evaluated the attitudes of patients with neurological diseases (NP) and healthy volunteers (HV) towards the donation of biological samples to a biobank for future research studies on neurological diseases, and limitations on the use of data, related to the requirements set by the General Data Protection Regulation (GDPR). The study involved a total of 1454 subjects, including 502 HVs and 952 NPs, recruited at Santa Lucia Foundation IRCCS, Rome, from 2020 to 2024. Results We found that (i) almost all subjects agreed with the participation in biobanking (ii) and authorization to genetic studies (HV = 99.1%; NP = 98.3%); Regarding the return of results, (iii) we found a statistically significant difference between NP and HV, the latter preferring not to be informed of potential results (HV = 43%; NP = 11.3%; p

Abstract Background Multiple sclerosis (MS) is a chronic and often disabling disease that impacts the central nervous system, leading to significant public health concerns. This study aimed to assess the level of awareness and knowledge of MS among the population of Tobruk, Libya. Methods A community-based cross-sectional study was conducted in Tobruk, Libya, during August 2023. A total of 1,427 participants were surveyed using the Multiple Sclerosis Knowledge Questionnaire (MSKQ-25). Data were collected via an online Google form and analyzed using RStudio and SPSS. The analysis included descriptive statistics, Chi-square tests, t-tests, Mann-Whitney tests, ANOVA, Kruskal-Wallis tests, and Pearson’s correlation coefficients. Results The study found a low level of MS awareness among participants, with a mean MSKQ-25 score of 8.32 ± 5.44. Significant differences in MS knowledge were observed between individuals with relatives who had MS and those without (p

Abstract Background Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. Methods An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. Results A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45–2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. Conclusions Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants.

Abstract Purpose Childhood cancer survivors (CCS) have an increased risk of developing late chronic diseases, which can be influenced by the cancer type and its treatment. These chronic diseases can be severe and disabling, typically emerging years to decades after treatment. These deficits negatively impact quality of life, intelligence quotient, and memory. This study investigated how much the cancer type and treatment could affect the neurological hospitalisations in the French Childhood Cancer Survivors Study (FCCSS). Methods We included 5579 childhood cancer survivors (CCS), diagnosed with solid tumours or lymphoma between 1945 and 2000, treated before 2001 and below the age of 21 years at initial treatment. The follow-up period was from 2006 to 2018. Hospitalisation data were obtained by linkage with the National Health Data System. We calculated the relative hospitalisation rate (RHRs) and absolute excess rate (AERs). Multivariable analyses were conducted using a Generalized Linear Model (GLM) with a Poisson distribution to estimate the association between neurological hospitalisation and patient characteristics. The expected number of hospitalisations served as an offset to compare the risk for FCCSS survivors with that of the reference population. Risk estimates were reported as relative risk (RR) with 95% confidence intervals. Results The hospitalisation rate for CCS was 114.2 per 10,000 person-years (PY), compared to 48.4 in the reference population. The highest hospitalisation rates were observed for epilepsy (AER = 27.1 per 10000 PY, 95%CI: 23.5–31.2 and RHR = 5.1, 95%CI 4.4–5.7). In multivariable analyses, central nervous system (CNS) tumours survivors had the highest relative risk (RR) of hospitalisation (RR = 9.4, 95%CI: 6.7–13.1) followed by neuroblastoma survivors (RR = 2.5, 95%CI: 1.7–3.7). In the whole population, survivors who received radiation to the head and neck had a significantly higher risk of hospitalisation (RR = 3.9, 95%CI: 3.3–4.7) compared to those who did not receive radiotherapy. Conclusions Head and neck irradiation was identified as a strong risk factor for hospitalisation. This underlines the importance of implementing specific neurologic surveillance programs for at-risk individuals.

Background: Sleep disorders significantly affect the quality of live and may impair cognitive development. Sleep disorders are reported to be common in chi ldr en wi th neurological diseases. However no report has evaluated the prevalence of sleep disorders among children chronic neurological diseases in Nigeria. This study therefore sort to determine the prevalence and types of sleep disorders among chi ldren wi th neurological diseases seen Child neurology clinic of University of Benin Teaching Hospital (UBTH), Benin City. Subjects and methods: This was a que s t ionna i r e ba s ed c ros s sectional study. Parents/caregivers of children attending the Child Neurology Clinic of UBTH were recruited and a structured questionnaire was administered to evaluate the presence of sleep disorders in the children they have brought to the clinic. Response scale ranged from never, rarely, occasional, frequent and very frequent. Children were judged to have sleep disorder if the symptom were present f requently or very frequently. Variables were aggregated as simple proportions and differences determine using chi-square test. Result:One hundred and fifty children aged 17years and below consisting of 98 (65.3%) males and 52 (34.7%) were evaluated. The most common sleep disorders found include restlessness during sleep 68.7%, frequent awakening 66.0%, snoring 57.3%, excessive day time sleepiness 53.3% and sleep walking among others. Sleep disorders were more common in boys than in girls and those aged 5 years and below than older children. Conclusion: Sleep disorders are very common among children with neurological diseases. These problems have great potential of fur ther impairing cognitive development and quality of life in these children.

Abstract Adult hippocampal neurogenesis (AHN) is affected by multiple factors, such as enriched environment, exercise, ageing, and neurodegenerative disorders. Neurodegenerative disorders can impair AHN, leading to progressive neuronal loss and cognitive decline. Compelling evidence suggests that individuals engaged in regular exercise exhibit higher production of proteins that are essential for AHN and memory. Interestingly, specific molecules that mediate the effects of exercise have shown effectiveness in promoting AHN and cognition in different transgenic animal models. Despite these advancements, the precise mechanisms by which exercise mimetics induce AHN remain partially understood. Recently, some novel exercise molecules have been tested and the underlying mechanisms have been proposed, involving intercommunications between multiple organs such as muscle-brain crosstalk, liver-brain crosstalk, and gut-brain crosstalk. In this review, we will discuss the current evidence regarding the effects and potential mechanisms of exercise mimetics on AHN and cognition in various neurological disorders. Opportunities, challenges, and future directions in this research field are also discussed.

Background: Multiple sclerosis (MS) is a chronic and often disabling disease that impacts the central nervous system, leading to significant public health concerns. This study aimed to assess the level of awareness and knowledge of MS among the population of Tobruk, Libya. Methods: A community-based cross-sectional study was conducted in Tobruk, Libya, during August 2023. A total of 1,427 participants were surveyed using the Multiple Sclerosis Knowledge Questionnaire (MSKQ-25). Data were collected via an online Google form and analyzed using RStudio and SPSS. The analysis included descriptive statistics, Chi-square tests, t-tests, Mann-Whitney tests, ANOVA, Kruskal-Wallis tests, and Pearson's correlation coefficients. Results: The study found a low level of MS awareness among participants, with a mean MSKQ-25 score of 8.32 ± 5.44. Significant differences in MS knowledge were observed between individuals with relatives who had MS and those without (p < 0.001), and between medical field students and students from other backgrounds (p < 0.001). No significant association was found between MS knowledge scores and marital status or educational levels. However, significant associations were observed between MS knowledge and age, gender, and financial status (p < 0.05 for all). The majority of participants lacked knowledge about genetics, etiology, and treatment of MS. Conclusion: The findings highlight a critical need for comprehensive public outreach and education programs to improve MS awareness in Tobruk, Libya. Health education initiatives focused on MS are essential for increasing community knowledge, facilitating early detection, and improving disease management. Further research is needed to understand the reasons for misinformation and to develop strategies for increasing awareness across the country. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that exposure to air pollution acts as a potential trigger for neurological diseases (NDs), yet the current knowledge regarding the impact of ambient nitrogen dioxide (NO2) on the patients with NDs remains limited. In this study, we conducted a time-series study to evaluate the association between short-term exposure to NO2 and hospital visits for NDs in Xinxiang, China. Methods: An over-dispersed Poisson generalized additive model was used to analyze the association between ambient NO2 concentrations and daily outpatient visits for NDs from January 1, 2015 to December 31, 2017. The model adjusted for meteorological factors, temporal trends, day of the week, and public holidays. The concentrations of air pollutants were collected from four air quality stations in Xinxiang. Results: A total of 38, 865 outpatient visits for NDs were retrieved during the study period. 86.5% of the patients were below the age of 65 years. It was revealed that a 10 µg/m3 increase in NO2 at lag 0 was associated with a significant rise of 1.50% (95% CI: 0.45–2.56%) in outpatient visits for NDs, which was stronger during the cold season. However, the overall results from stratified analyses did not reach statistical significance. Conclusions: Short-term exposure to NO2 is associated with increased outpatient visits for NDs. These findings underscore the need for implementing mitigating measures to reduce the neurological health effects of air pollutants. [ABSTRACT FROM AUTHOR]

Background: The growing diffusion of artificial intelligence, data science and digital health has highlighted the role of collection of data and biological samples, thus raising legal and ethical concerns regarding its use and dissemination. Further, the expansion of biobanking, from the basic collection of frozen specimens to the virtual biobanks of specimens and associated data that exist today, has given a revolutionary potential on healthcare systems, particularly in the field of neurological diseases, due to the inaccessibility of central nervous system and the need of non-invasive investigation approaches. Informed Consent (IC) is considered mandatory in all research studies and specimen collections, and must specifically take into account the ethical respect to the individuals to whom the used biological material and data belong. Methods: We evaluated the attitudes of patients with neurological diseases (NP) and healthy volunteers (HV) towards the donation of biological samples to a biobank for future research studies on neurological diseases, and limitations on the use of data, related to the requirements set by the General Data Protection Regulation (GDPR). The study involved a total of 1454 subjects, including 502 HVs and 952 NPs, recruited at Santa Lucia Foundation IRCCS, Rome, from 2020 to 2024. Results: We found that (i) almost all subjects agreed with the participation in biobanking (ii) and authorization to genetic studies (HV = 99.1%; NP = 98.3%); Regarding the return of results, (iii) we found a statistically significant difference between NP and HV, the latter preferring not to be informed of potential results (HV = 43%; NP = 11.3%; p < 0.0001); (iv) a small number limited the sharing inside European Union (EU) (HV = 4.6%; NP = 6.6%), whereas patients were more likely to refuse transfer outside EU (HV = 7.4%; NP = 10.7% p = 0.05); (v) nearly all patients agreed with the use of additional health data from EMR for research purposes (98.9%). Conclusions: Consent for the donation of material for research purposes is crucial for biobanking and biomedical research studies that use biological material of human origin. Here, we have shown that choices regarding participation in a neurological biobank can be different between HVs and NPs, even if the benefit for research and scientific progress is recognized. NP have a strong interest in being informed of possible results but limit sharing of samples, highlighting a perception of greater individual or relative benefit, while HV prefer a wide dissemination and sharing of data but not to have the return of the results, favoring a possible benefit for society and knowledge. The results underline the need to carefully manage biological material and data collected in biobanks, in compliance with the GDPR and the specific requests of donors. [ABSTRACT FROM AUTHOR]

The prevalence of neurological dieases, including neurodegenerative, neurotraumatic disorders, and neuroinflammatory conditions, has been rising due to global population and aging demographics. A key factor in the pathogenesis of these disorders is the hyperaccumulation of reactive oxygen and nitrogen species (RONS). Nanozymes have emerged as promising candidates for neurotherapeutic applications owing to their exceptional catalytic activity and stability. Of particular note is their ability to cross the blood‐brain barrier and counteract the production of reactive oxygen species via their enzyme‐mimicking characteristics. In this review, the latest advancements and theoretical knowledge in this research domain are summarized. Using the inherent functionalities of the Web of Science and bibliometric methodologies, annual publication trends are identified and extensively explored the most researched topics and neurological disorders in this field. The antioxidant reduction chemistry of the nanozymes is discussed, highlighting their ability to mimic natural oxidoreductase activity and inhibit RONS production at the source. Moreover, this review delves into the current limitations and future prospects of these mechanisms in addressing neurological disorders. The significant benefits and recent developments in the use of RONS‐regulating nanozymes for the treatment of neurological diseases are emphasized, offering insights into their therapeutic applications and broader implications for neurology. [ABSTRACT FROM AUTHOR]

The enteric nervous system (ENS) is a fundamental component of the gastrointestinal system, composed of a vast network of neurons and glial cells. It operates autonomously but is interconnected with the central nervous system (CNS) through the vagus nerve. This communication, known as the gut–brain axis, influences the bidirectional communication between the brain and the gut. Background/Objectives: This study aimed to review neurological pathologies related to the ENS. Methods: To this end, a comprehensive literature search was conducted in the "PubMed" database. Articles available in "free format" were selected, applying the filters "Humans" and limiting the search to publications from the last ten years. Results: The ENS has been linked to various neurological diseases, from autism spectrum disorder to Parkinson's disease including neurological infection with the varicella zoster virus (VZV), even sharing pathologies with the CNS. This finding suggests that the ENS could serve as an early diagnostic marker or therapeutic target for neurological diseases. Gastrointestinal symptoms often precede CNS symptoms, and the ENS's accessibility aids in diagnosis and treatment. Parkinson's patients may show intestinal lesions up to twenty years before CNS symptoms, underscoring the potential for early diagnosis. However, challenges include developing standardized diagnostic protocols and the uneven distribution of dopaminergic neurons in the ENS. Continued research is needed to explore the ENS's potential in improving disease prognosis. Conclusions: The ENS is a promising area for early diagnosis and therapeutic development. Nevertheless, it is essential to continue research in this area, especially to gain a deeper understanding of its organization, function, and regenerative capacity. [ABSTRACT FROM AUTHOR]

The potassium–chloride cotransporter KCC2 is the main extruder of Cl- in neurons. It plays a fundamental role in the activity of the inhibitory neurotransmitters (GABA and glycine) since low levels of KCC2 promote intracellular Cl- accumulation, leading to the depolarizing activity of GABA and glycine. The downregulation of this cotransporter occurs in neurological disorders characterized by hyperexcitability, such as epilepsy, neuropathic pain, and spasticity. KCC2 is also downregulated after axotomy. If muscle reinnervation is allowed, the KCC2 levels recover in motoneurons. Therefore, we argued that target-derived neurotrophic factors might be involved in the regulation of KCC2 expression. For this purpose, we performed the axotomy of extraocular motoneurons via the monocular enucleation of adult rats, and a pellet containing either VEGF or BDNF was chronically implanted in the orbit. Double confocal immunofluorescence of choline acetyl-transferase (ChAT) and KCC2 was carried out in the brainstem sections. Axotomy led to a KCC2 decrease in the neuropil and somata of extraocular motoneurons, peaking at 15 days post-lesion, with the exception of the abducens motoneuron somata. VEGF administration prevented the axotomy-induced KCC2 downregulation. By contrast, BDNF either maintained or reduced the KCC2 levels following axotomy, suggesting that BDNF is involved in the axotomy-induced KCC2 downregulation in extraocular motoneurons. The finding that VEGF prevents KCC2 decrease opens up new possibilities for the treatment of neurological disorders coursing with neuronal hyperactivity due to KCC2 downregulation. [ABSTRACT FROM AUTHOR]

The KCNE2 protein is encoded by the kcne2 gene and is a member of the KCNE protein family, also known as the MinK-related protein 1 (MiRP1). It is mostly present in the epicardium of the heart and gastric mucosa, and it is also found in the thyroid, pancreatic islets, liver and lung, among other locations, to a lesser extent. It is involved in numerous physiological processes because of its ubiquitous expression and partnering promiscuity, including the modulation of voltage-dependent potassium and calcium channels involved in cardiac action potential repolarization, and regulation of secretory processes in multiple epithelia, such as gastric acid secretion, thyroid hormone synthesis, generation and secretion of cerebrospinal fluid. Mutations in the KCNE2 gene or aberrant expression of the protein may play a critical role in cardiovascular, neurological, metabolic and multisystem disorders. This article provides an overview of the advancements made in understanding the physiological functions in organismal homeostasis and the pathophysiological consequences of KCNE2 in multisystem diseases. [ABSTRACT FROM AUTHOR]

Neurological monogenic loss-of-function diseases are hereditary disorders resulting from gene mutations that decrease or abolish the normal function of the encoded protein. These conditions pose significant therapeutic challenges, which may be resolved through the development of innovative therapeutic strategies. RNA-based technologies, such as mRNA replacement therapy, have emerged as promising and increasingly viable treatments. Notably, mRNA therapy exhibits significant potential as a mutation-agnostic approach that can address virtually any monogenic loss-of-function disease. Therapeutic mRNA carries the information for a healthy copy of the defective protein, bypassing the problem of targeting specific genetic variants. Moreover, unlike conventional gene therapy, mRNA-based drugs are delivered through a simplified process that requires only transfer to the cytoplasm, thereby reducing the mutagenic risks related to DNA integration. Additionally, mRNA therapy exerts a transient effect on target cells, minimizing the risk of long-term unintended consequences. The remarkable success of mRNA technology for developing coronavirus disease 2019 vaccines has rekindled interest in mRNA as a cost-effective method for delivering therapeutic proteins. However, further optimization is required to enhance mRNA delivery, particularly to the CNS, while minimizing adverse drug reactions and toxicity. In this comprehensive review, we delve into past, present and ongoing applications of mRNA therapy for neurological monogenic loss-of-function diseases. We also discuss the promises and potential challenges presented by mRNA therapeutics in this rapidly advancing field. Ultimately, we underscore the full potential of mRNA therapy as a game-changing therapeutic approach for neurological disorders. [ABSTRACT FROM AUTHOR]

Modern medicine now has the capacity to improve therapy for many human diseases by introducing adult somatic stem cells that can repair or replace defective or damaged tissues. However, the area is still in an early phase of development, so all new applications must be carefully designed for maximal safety as well as effectiveness. [ABSTRACT FROM AUTHOR]

Observational studies have suggested that SARS-CoV-2 infection increases the risk of neurological diseases, but it remains unclear whether the association is causal. The present study aims to evaluate the causal relationships between SARS-CoV-2 infections and neurological diseases and analyzes the potential routes of SARS-CoV-2 entry at the cellular level. We performed Mendelian randomization (MR) analysis with CAUSE method to investigate causal relationship of SARS-CoV-2 infections with neurological diseases. Then, we conducted single-cell RNA sequencing (scRNA-seq) analysis to obtain evidence of potential neuroinvasion routes by measuring SARS-CoV-2 receptor expression in specific cell subtypes. Fast gene set enrichment analysis (fGSEA) was further performed to assess the pathogenesis of related diseases. The results showed that the COVID-19 is causally associated with manic (delta_elpd, − 0.1300, Z-score: − 2.4; P = 0.0082) and epilepsy (delta_elpd: − 2.20, Z-score: − 1.80; P = 0.038). However, no significant effects were observed for COVID-19 on other traits. Moreover, there are 23 cell subtypes identified through the scRNA-seq transcriptomics data of epilepsy, and SARS-CoV-2 receptor TTYH2 was found to be specifically expressed in oligodendrocyte and astrocyte cell subtypes. Furthermore, fGSEA analysis showed that the cell subtypes with receptor-specific expression was related to methylation of lysine 27 on histone H3 (H3K27ME3), neuronal system, aging brain, neurogenesis, and neuron projection. In summary, this study shows causal links between SARS-CoV-2 infections and neurological disorders such as epilepsy and manic, supported by MR and scRNA-seq analysis. These results should be considered in further studies and public health measures on COVID-19 and neurological diseases. [ABSTRACT FROM AUTHOR]

Many human diseases, such as malignant tumors and neurological diseases, have a complex pathophysiological etiology, often accompanied by aberrant epigenetic changes including various histone modifications. Plant homologous domain finger protein 8 (PHF8), also known as lysine-specific demethylase 7B (KDM7B), is a critical histone lysine demethylase (KDM) playing an important role in epigenetic modification. Characterized by the zinc finger plant homology domain (PHD) and the Jumonji C (JmjC) domain, PHF8 preferentially binds to H3K4me3 and erases repressive methyl marks, including H3K9me1/2, H3K27me1, and H4K20me1. PHF8 is indispensable for developmental processes and the loss of PHF8 enzyme activity is linked to neurodevelopmental disorders. Moreover, increasing evidence shows that PHF8 is highly expressed in multiple tumors as an oncogenic factor. These findings indicate that studying the role of PHF8 will facilitate the development of novel therapeutic agents by the manipulation of PHF8 demethylation activity. Herein, we summarize the current knowledge of PHF8 about its structure and demethylation activity and its involvement in development and human diseases, with an emphasis on nervous system disorders and cancer. This review will update our understanding of PHF8 and promote the clinical transformation of its predictive and therapeutic value. [ABSTRACT FROM AUTHOR]

Background: Neurological diseases resulting from nervous system injuries can significantly impact nutritional status and the physical and cognitive capacities necessary for maintaining a sufficient diet. This study focuses on primary nutritional therapies for neurological illnesses. Methods: An integrative literature review was conducted using three databases: PePSIC, Medline, and LILACS. A comprehensive search strategy was employed, incorporating descriptors such as neuropathies, nutritional therapy, efficacy, and side effects. Results: After applying inclusion criteria, 175 relevant items were identified. While traditional medical interventions for neurological conditions typically involve medication, food therapy has shown promise in enhancing clinical outcomes and alleviating symptoms for certain diseases. Specifically, food therapy has been effective in improving the prognosis of adrenoleukodystrophy and mitigating symptoms of Wernicke-Korsakoff syndrome and epilepsy. Conclusion: Patients with neurological illnesses, such as adrenoleukodystrophy, Wernicke-Korsakoff syndrome, and epilepsy, may benefit from dietary interventions to improve prognosis and alleviate symptoms. Therefore, healthcare professionals should consider incorporating food therapy into the treatment plans for these conditions to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Intrinsic biological clocks drive the circadian rhythm, which coordinates the physiological and pathophysiological processes in the body. Recently, a bidirectional relationship between circadian rhythms and several neurological diseases has been reported. Neurological diseases can lead to the disruption of circadian homeostasis, thereby increasing disease severity. Therefore, optimizing the current treatments through circadian-based approaches, including adjusted dosing, changing lifestyle, and targeted interventions, offer a promising opportunity for better clinical outcomes and precision medicine. In this review, we provide detailed implications of the circadian rhythm in neurological diseases through bench-to-bedside approaches. Furthermore, based on the unsatisfactory clinical outcomes, we critically discuss the potential of circadian-based interventions, which may encourage more studies in this discipline, with the hope of improving treatment efficacy in neurological diseases. [ABSTRACT FROM AUTHOR]

Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. It is well known that PKM2 plays a vital role in the proliferation of tumor cells. However, PKM2 can also exert its biological functions by mediating multiple signaling pathways in neurological diseases, such as Alzheimer's disease (AD), cognitive dysfunction, ischemic stroke, post-stroke depression, cerebral small-vessel disease, hypoxic-ischemic encephalopathy, traumatic brain injury, spinal cord injury, Parkinson's disease (PD), epilepsy, neuropathic pain, and autoimmune diseases. In these diseases, PKM2 can exert various biological functions, including regulation of glycolysis, inflammatory responses, apoptosis, proliferation of cells, oxidative stress, mitochondrial dysfunction, or pathological autoimmune responses. Moreover, the complexity of PKM2's biological characteristics determines the diversity of its biological functions. However, the role of PKM2 is not entirely the same in different diseases or cells, which is related to its oligomerization, subcellular localization, and post-translational modifications. This article will focus on the biological characteristics of PKM2, the regulation of PKM2 expression, and the biological role of PKM2 in neurological diseases. With this review, we hope to have a better understanding of the molecular mechanisms of PKM2, which may help researchers develop therapeutic strategies in clinic. [ABSTRACT FROM AUTHOR]

lipid rafts microregions, also known as lipid rafts (LR), are a type of functional region on the cell membrane that is rich in sugars, lipids, sphingolipids, and cholesterol. LR is an important participant in the immune and inflammatory processes of the body. Diseases such as cancer, neurological disorders, infectious diseases, and cardiovascular diseases are often accompanied by pathological manifestations such as dysregulation or deficiency of LR. This article provides an overview of the structure and composition of LR at the cellular and molecular levels, explores the methods and mechanisms of targeted LR treatment for related diseases, and explores their correlation. It compares the differences in the efficacy of traditional Chinese medicine and Western medicine based on LR mechanism, in order to provide new ideas for the research and clinical treatment of related diseases. [ABSTRACT FROM AUTHOR]