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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which blocking the early steps of extracellular misfolded amyloid-β (Aβ) aggregation is a promising therapeutic approach. However, the pathological features of AD progression include the accumulation of intracellular tau protein, membrane-catalyzed cell death and the abnormal deposition of Aβ. Here, we focus on anti-amyloid breaker peptides derived from the Aβ sequence and non-Aβ-based peptides containing both natural and modified amino acids. Critical aspects of the breaker peptides include N-methylation, conformational restriction through cyclization, incorporation of unnatural amino acid, fluorinated molecules, polymeric nanoparticles and PEGylation. This review confers a general idea of such breaker peptides with in vitro and in vivo studies, which may advance our understanding of AD pathology and develop an effective treatment strategy against AD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that currently has no cure. The aged population is growing globally, creating an urgent need for more promising therapies for this debilitating disease. Much effort has been made in recent decades, and the field is highly dynamic, with numerous trials. The main focus of these trials includes disease modification and symptomatic treatment. Some have shown beneficial outcomes, while others have shown no significant benefits. Here, we cover the outcome of recently published AD clinical trials, as well as the mechanism of action of these therapeutical agents, to re-think drug development strategies and directions for future studies.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that exerts a huge burden on our society. The occurrence of this neurodegenerative disease has been increasing day-by-day. PD can be a serious concern if the patients are left untreated. However, conventional treatment has many side-effects and less bioavailability in the brain. Therefore, the necessary measurement is required to solve the limitations of PD treatment. Nanotechnology has made a major contribution to comprehend PD pathogenesis. Nanotechnology can provide efficient therapies that have reduced side-effects and increased bioavailability in the brain. This review emphasizes the emerging promise of nanoparticle-based treatment, drug delivery, and other therapeutic approaches for PD. Besides, the advantages of different approaches on nanotechnology platforms are far better over conventional therapy in the treatment of PD.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects a sizable fraction of the population and degrades the quality of life. Levodopamine (L-Dopa) is the first-line trea...

Parkinson’s disease (PD) is a second most progressive neurodegenerative disorder. Millions of people across the world are affected with this disease. In recent days, there are significant research has been reported for the screening of PD using Dysphonia features. In this study, a new weights generation method named as Kernel Fuzzy C-means Ratio based on different clustering technique (KFCM, FCM and KCM) has been proposed. The main aim of this work is to transform non-separable speech features in the dataset to a linearly separable such that the classification can be enhanced. In classification stage, six different classifiers are used to classify the weighted data and significant improvement in sensitivity, accuracy and specificity parameters are recorded.

Introduction Degenerative cervical myelopathy (DCM) is a progressive neurodegenerative disorder. DCM is common (estimated prevalence, 2% of adults) and significantly impacts quality of life. The AO Spine RECODE-DCM (Research Objectives and Common Data Elements in DCM) project has recently established the top research priorities for DCM. This article examines the extent to which existing research activity aligns with the established research priorities. Methods A systematic review of MEDLINE and Embase for “Cervical” AND “Myelopathy” was conducted following PRISMA guidelines. Full-text papers in English, exclusively studying DCM, published between January 1, 1995 and August 08, 2020 were considered eligible. Extracted data for each study included authors, journal, year of publication, location, sample size and study design. Each study was then analysed for alignment to the established research priorities. Results In total, 2261 papers with a total of 1,323,979 patients were included. Japan published more papers (625) than any other country. Moreover, 2005 (89%) of 2261 papers were aligned to at least one research priority. The alignment of papers to the different research priorities was unequal, with 1060 papers on the most researched priority alone (#15, predictors of outcome after treatment), but only 64 total papers on the least-researched 10 priorities. The comparative growth of research in the different priorities was also unequal, with some priorities growing and others plateauing over the past 5 years. Discussion Research activity in DCM continues to grow, and the focus of this research remains on surgery. The established research priorities therefore represent a new direction for the field.

Alzheimer’s Disease (AD), a progressive neurodegenerative disorder linked to increasing age, is the primary cause of dementia in the world. Clinically, it is characterized by cognitive impairments, progressive memory deficits and diminished learning ability. Despite the comprehensive research in AD, none of the existing treatments prevents the onset and progression of the disease. The use of medicinal plants is a fundamental component of the African traditional healthcare system due to its accessibility and affordability in many parts of rural Africa. However, there is a dearth of an updated comprehensive compilation of potential medicinal plants from the African continent commonly used in the management of AD. The primary focus of the present article is to review evidence from selected African plants in experimental and preclinical studies which have promising prospects to be developed as novel therapeutic agents for the treatment of AD. To achieve this, major scientific databases such as Science Direct, Pubmed, Scopus, Web of Science and Google Scholar have been searched to investigate and gather information on African traditional medicinal plants useful for the treatment of cognitive deficits, memory impairments and AD. Our search results showed several commonly used medicinal plants and their possible mechanisms of action including inhibition of acetylcholinesterase activity, modification of Aβ processing, protection against oxidative stress and regulation of antioxidant enzymes activity. This review therefore provides a compilation of medicinal plants that could be further studied for their bioactive constituents; these may become safe, effective and novel therapeutic candidates for the treatment of AD.

Alzheimer's disease (AD) is a pervasive, relentlessly progressive neurodegenerative disorder that includes both hereditary and sporadic forms linked by common underlying neuropathologic changes and neuropsychological manifestations. While a clinical diagnosis is often made on the basis of initial memory dysfunction that progresses to involve multiple cognitive domains, definitive diagnosis requires autopsy examination of the brain to identify amyloid plaques and neurofibrillary degeneration. Over the past 100 years, there has been remarkable progress in our understanding of the underlying pathophysiologic processes, pathologic changes, and clinical phenotypes of AD, largely because genetic pathways that include but expand beyond amyloid processing have been uncovered. This review discusses the current state of understanding of the genetics of AD with a focus on how these advances are both shaping our understanding of the disease and informing novel avenues and approaches for development of potential therapeutic targets.

Alzheimer disease is a progressive neurodegenerative disorder, mainly affecting older people, which severely impairs patients' quality of life. In the recent years, the number of affected individuals has seen a rapid increase. It is estimated that up to 107 million subjects will be affected by 2050 worldwide. Research in this area has revealed a lot about the biological and environmental underpinnings of Alzheimer, especially its correlation with β-Amyloid and Tau related mechanics; however, the precise molecular events and biological pathways behind the disease are yet to be discovered. In this review, we focus our attention on the biological mechanics that may lie behind Alzheimer development. In particular, we briefly describe the genetic elements and discuss about specific biological processes potentially associated with the disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects 50 million people worldwide. The current medicines have modest benefits in preventing or curing AD. Thus, it is urgent to discover drugs with the potential to change the progression of the disease. The primary clinical symptoms are memory loss and anxiety, while the critical pathological characteristics are Aβ plaques and hyperphosphorylated tau tangles. In this study, isobavachalcone (ISO), isolated from Psoralea corylifolia, was administered to 3×Tg-AD mice. It has been shown that this compound could significantly improve anxiety, memory and recognition deficits in the AD mice, attenuate the accumulation of Aβ oligomers, reduce the hyperphosphorylation of tau, and prevent the production of tau filaments. The metabolomic analysis implicates that the most probable pathways affected by ISO were bile secretion, tyrosine metabolism, and purine metabolism. In summary, ISO possesses the potential for further development as a drug candidate for AD.

Juvenile CLN3 disease, the most prevalent form of Batten disease, is a progressive neurodegenerative disorder resulting from mutations in the CLN3 gene. The objective of this study was to design an ophthalmic rating scale for CLN3 disease in order to quantify disease progression.Retrospective, cross-sectional study.Patients underwent ophthalmic evaluations including visual testing, optical coherence tomography and fundus imaging. Patients were also assessed using the Hamburg Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) scoring system. Ophthalmic findings were divided into grades of severity ranging from 0 to 3, and the association between the extent of ocular disease and neurological function and age was assessed.Forty-two eyes of 21 patients were included. The mean age at the time of examination was 13.2 years (range, 5.3-21.9 years). The mean ophthalmic severity grade was 2.4 (range, 0-3). The mean neurological severity score was 9.9 (range, 4-14). Ophthalmic manifestations increased in severity with increasing age of the patients (r = -0.84; P.001), and a strong correlation was found between the CLN3 ophthalmic rating scale score and the Hamburg JNCL score (r = 0.83; P.001).Ophthalmic manifestations of CLN3 disease correlate closely with the severity of neurological symptoms and age of the patient. The newly established Hamburg CLN3 ophthalmic rating scale may serve as an objective marker of ocular disease severity and progression and may be valuable tool for the evaluation of novel therapeutic strategies for CLN3 disease.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Aging is the most significant risk factor for late-onset AD. The age-associated changes in the immune system are termed immunosenescence. A close connection between immunosenescence and AD is increasingly recognized. This article provides an overview of immunosenescence and evidence for its role in the pathogenesis of AD and possible mechanisms as well as the outlook for drug development.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that results from the accumulation of plaques by cleaved Aβ42 peptides as well as neurofibrillary tangles of tau proteins. This accumulation triggers a complex cascade of cytotoxic, neuroinflammatory, and oxidative stresses that lead to neuronal death throughout the progression of the disease. Much of research in AD focused on the 2 pathologic proteins. Interestingly, another form of dementia with similar clinical manifestations of AD, but preferentially affected much older individuals, was termed as limbic-predominant age-related transactive response DNA-binding protein 43 (TDP-43) encephalopathy (LATE) and involved the cytotoxic intraneuronal deposition of phosphorylated TDP-43. TDP-43 proteinopathy was also found to be involved in AD pathology leading to the possibility that AD and LATE may share a common upstream etiology. This paper discusses the roles molecular pathways known in AD may have on influencing TDP-43 proteinopathy and the development of AD, LATE, or the 2 being comorbid with each other.

Achalasia is a progressive neurodegenerative disorder characterized by failure of relaxation of the lower esophageal sphincter (LES) and altered motility of the esophagus. The traditional, highly effective, surgical approach to relieve obstruction at the LES includes cardiomyotomy. Fundoplication is added to decrease risk of postoperative reflux. Per oral endoscopic myotomy is a new endoscopic procedure that allows division of the LES via transoral route. It has several advantages including less invasiveness, cosmesis, and tailored approach to the length on the myotomy. However, it is associated with increased rate of post-procedural reflux. Various endoscopic interventions are used to address this problem.

Prion disease is a rapidly progressive neurodegenerative disorder caused by misfolding and aggregation of the prion protein (PrP), and there are currently no therapeutic options. PrP ligands could theoretically antagonize prion formation by protecting the native protein from misfolding or by targeting it for degradation, but no validated small-molecule binders have been discovered to date. We deployed a variety of screening methods in an effort to discover binders of PrP, including 19F-observed and saturation transfer difference (STD) nuclear magnetic resonance (NMR) spectroscopy, differential scanning fluorimetry (DSF), DNA-encoded library selection, and in silico screening. A single benzimidazole compound was confirmed in concentration-response, but affinity was very weak (Kd > 1 mM), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. While orthogonal binder discovery methods could yield high affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disorder. A defining hallmark of the AD brain is the presence of intraneuronal neurofibrillary tangles (NFTs) which are made of up of abnormally modified tau, with aberrant phosphorylation being the most studied posttranslational modification (PTM). Although the accumulation of tau as NFTs is an invariant feature of the AD brain, it has become evident that these insoluble aggregates are likely not the primary pathogenic form of tau, rather soluble forms of tau with abnormal PTMs are the mediators of toxicity. The most prevalent PTMs on tau is phosphorylation, with the abnormal modification of specific residues on tau playing a key role in its toxicity. Even though it is widely accepted that tau with aberrant PTMs facilitate neurodegeneration, the precise cellular mechanisms remain unknown. Nonetheless, there is an evolving conceptual framework that an important contributing factor may be selective pathological tau species compromising mitochondrial biology. Understanding the mechanisms by which tau with site specific PTMs impact mitochondria is crucial for understanding the role tau plays in AD. Here we provide a brief introduction to tau and its phosphorylation and function in a physiological context, followed by a discussion of the impact of soluble phosphorylated tau species on neuronal processes in general and mitochondria more specifically. We also discuss how therapeutic strategies that attenuate pathological tau species in combination with treatments that improve mitochondrial biology could be a potential therapeutic avenue to mitigate disease progression in AD and other tauopathies.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting both the upper and lower motor neurons. Although ALS typically leads to death within 3 to 5 years after initial symptom onset, approximately 10% of patients with ALS live more than 10 years after symptom onset. We set out to determine similarities and differences in clinical presentation and neuropathology in persons with ALS with long vs. those with standard duration. Participants were United States military Veterans with a pathologically confirmed diagnosis of ALS (n = 179), dichotomized into standard duration (

Huntington’s Disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by severe symptoms, including motor impairment, cognitive decline, and psychiatric alterations. Several systems, molecules, and mediators have been associated with the pathophysiology of HD. Among these, there is the Renin-Angiotensin System (RAS), a peptide hormone system that has been associated with the pathology of neuropsychiatric and neurodegenerative disorders. Important alterations in this system have been demonstrated in HD. However, the role of RAS components in HD is still unclear and needs further investigation. Nonetheless, modulation of the RAS components may represent a potential therapeutic strategy for the treatment of HD.

The P300-based brain-computer interface speller can provide motor independent communication to individuals with amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disorder that affects the motor system. P300 amplitude stability is critical for operation of the P300 speller. The P300 has good long-term stability, but to our knowledge, short-term habituation in the P300 speller has not been studied. In the current study, 15 participants: 8 ALS patients and 7 age-matched healthy volunteers (HVs), used 2 versions of P300 spellers, Face speller and Flash speller, each for 30 minutes. The ALS group performed as well as the HVs in both spellers and HVs did better with the Face speller than Flash speller while the ALS group performed equally well in both spellers. Neither intra-run P300 habituation nor inter-run P300 habituation was found. The P300 speller could be a reliable communication device for individuals with ALS.

Alzheimer's disease is a progressive neurodegenerative disorder and patients suffer from memory loss, a decline in language skill and impairment in other cognitive functions. In the cholinergic hypothesis, dysfunction of cholinergic neurons especially in the hippocampus and cerebral cortex contributes to cognitive decline in patients. So agents that enhance acetylcholine concentration could improve cognitive function. AChEIs are among the most studied anti-Alzheimer agents. Galbanic acid as a natural compound with a sesquiterpene coumarin scaffold is a weak inhibitor of AChE. In the present contribution, we discussed the impact of carboxylic group ionization on inhibitory effects. We performed

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that mostly strikes the elderly. However, the exact molecular and cellular pathogenesis of AD, especially the dynamic changes of neurons during disease progression, remains poorly understood. Here we used single-nucleus RNA sequencing (snRNA-seq) to access the transcriptional changes of hippocampal neurons in APP23 mouse model of AD. We performed snRNA-seq using a modified Smart-seq2 technique on 3,280 neuronal nuclei from the hippocampus of young and aged APP23 and control mice and identified four distinct subpopulations. Comparative transcriptional analysis showed multiple changes in different subtypes of hippocampal neurons of APP23 mice in comparison to control mice, as well as the transcriptional changes in these neurons during disease progression. Our findings revealed multiple neuronal subtype-specific transcriptional changes that may lead to targets for future studies of AD.

Aims Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Previous studies have demonstrated abnormalities in functional connectivity (FC) of AD under the assumption that FC is stationary during scanning. However, studies on the FC dynamics of AD, which may provide more insightful perspectives in understanding the neural mechanisms of AD, remain largely unknown. Methods Combining the sliding‐window approach and the k‐means algorithm, we identified three reoccurring dynamic FC states from resting‐state fMRI data of 26 AD and 26 healthy controls. The between‐group differences both in FC states and in regional temporal variability were calculated, followed by a correlation analysis of these differences with cognitive performances of AD patients. Results We identified three reoccurring FC states and found abnormal FC mainly in the frontal and temporal cortices. The temporal properties of FC states were changed in AD as characterized by decreased dwell time in State I and increased dwell time in State II. Besides, we found decreased regional temporal variability mainly in the somatomotor, temporal and parietal regions. Disrupted dynamic FC was significantly correlated with cognitive performances of AD patients. Conclusion Our findings suggest abnormal dynamic FC in AD patients, which provides novel insights for understanding the pathophysiological mechanisms of AD.

Alzheimer's Disease is a complex progressive neurodegenerative disorder characterized by neurofibrillary tangles and senile plaques in various parts of the brain particularly cerebral cortex affecting memory and cognition. Nuclear receptors such as Peroxisome proliferator-activated receptor γ [PPAR-γ] is reported to have a role in lipid and glucose homeostasis in the brain, reduces the synthesis of Aβ (beta-amyloid plaques) and also regulates mitochondrial biogenesis and inhibit the neuro-inflammation, which contributes for the improvement in the cognitive function in AD. Hence PPAR-γ is one of the newer targets for the researchers to understand the pathology of AD and to evolve the novel strategy to retard/reverse the progression of AD. PPAR-γ agonists such as Rosiglitazone and Pioglitazone have shown promising results in AD by decreasing neuro-inflammation and restoring glucose dysmetabolism leading to a reduction in neuronal deterioration. These agonists possess poor blood-brain permeability and are poor candidates for clinical use in AD. Therefore, search, design, and development for new PPAR- γ agonists with improved BBB penetration ability are imperative. The present work deals with the use of computational tools and techniques such as molecular docking, molecular dynamics to discover PPAR-γ agonists from the unexplored Seaweed Metabolite Database and predicts it's toxicological and physiochemical profile, thereby saving time and resources. Out of 1,110 seaweed compounds, the hit molecule BS052 displayed a strong binding affinity towards PPAR-γ, which possessed better lipid solubility indicating the potential to be considered as a PPAR-γ agonist, which may be useful in the management of AD.Communicated by Ramaswamy H. Sarma.

Over the past decade, concern for negative outcomes associated with concussive brain trauma has grown immensely. These neuropathologic changes, termed chronic traumatic encephalopathy (CTE), have been linked to patients who exhibit neuropsychiatric symptoms and have experienced repetitive brain trauma. Recent publicity has brought about renewed interest in this progressive neurodegenerative disorder. This article will share the advances that have been made with CTE.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and a leading cause of dementia in the elderly. AD initially presents as mild cognitive impairment (MCI); later, as AD progresses, memory and cognition are destroyed, preventing the ability to carry out activities of daily living. The primary care provider may be the first to suspect MCI, and screening tests can help with diagnosis. Development of drugs for cognitive decline in AD has been slow; however new therapies are in the pipeline and discovery of biomarkers make early diagnosis and future treatment of AD hopeful.

Introduction: Familial isolated deficiency of vitamin E (VED or AVED; MIM #277460) is a progressive neurodegenerative disorder resembling Friedreich ataxia. It is caused by the deficiency of α-tocopherol transfer protein that prevents patients from retaining vitamin E. Oral vitamin E supplements are an accepted treatment, but detailed dosage recommendations and reports on long-term therapeutic results are scarce. Methods: The first patient with VED was discovered at our institution at the age of 12 years and has since been followed with clinical, neurophysiological, neuroradiological, and biochemical investigations to his present age of 52 years. For the last 36 years, the patient has scrupulously followed a custom-made high-dose vitamin E supplement regimen that we devised on the basis of studies of his metabolism of vitamin E. Results: Over the long period of observation, the patient has remained in good general health and has not shown progression of neurological symptoms and signs. His vitamin E plasma levels were always moderately above the normal range. During short interruptions of vitamin E supplements, vitamin E levels fell rapidly, even after years of massive supplementation. Discussion: In this VED patient, a specified and carefully controlled high-dose vitamin E therapy has prevented any recognizable progression of the neurodegenerative process over more than 3 decades of observation.

Ex vivo X-ray phase contrast tomography of amyotrophic lateral sclerosis of a SOD1G93A mouse model is presented. Quantification of neuronal and vascular alteration in the central nervous system is described., Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons. Pre-clinical studies drive the development of animal models that well mimic ALS disorder and enable both the dissection of disease processes and an early assessment of therapy efficacy. A comprehensive knowledge of neuronal and vascular lesions in the brain and spinal cord is an essential factor to understand the development of the disease. Spatial resolution and bidimensional imaging are important drawbacks limiting current neuroimaging tools, while neuropathology relies on protocols that may alter tissue chemistry and structure. In contrast, recent ex vivo studies in mice demonstrated that X-ray phase-contrast tomography enables study of the 3D distribution of both vasculature and neuronal networks, without sample sectioning or use of staining. Here we present our findings on ex vivo SOD1G93A ALS mice spinal cord at a micrometric scale. An unprecedented direct quantification of neuro-vascular alterations at different stages of the disease is shown.

Nodding syndrome (NS) is a progressive encephalopathy of children and adolescents characterized by seizures, including periodic vertical head nodding. Epidemic NS, which has affected parts of East Africa, appears to have clinical overlap with sub-Saharan Nakalanga syndrome (NLS), a brain disorder associated with pituitary dwarfism that appears to have a patchy distribution across sub-Sahara. Clinical stages of NS include inattention and blank stares, vertical head nodding, convulsive seizures, multiple impairments, and severe cognitive and motorsystem disability, including features suggesting parkinsonism. Head nodding episodes occur in clusters with an electrographic correlate of diffuse high-amplitude slow waves followed by an electrodecremental pattern with superimposed diffuse fast activity. Brain imaging reveals differing degrees of cerebral cortical and cerebellar atrophy. Brains of NS-affected children with mild frontotemporal cortical atrophy display neurofibrillary pathology and dystrophic neurites immunopositive for tau, consistent with a progressive neurodegenerative disorder. The etiology of NS and NLS appears to be dominated by environmental factors, including malnutrition, displacement, and nematode infection, but the specific cause is unknown.

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by an imbalance between the production and clearance of amyloid-β (Aβ) species. AD not only influences the life quality of the patients but also heavily burdens the families and society. Therefore, it is an urgent mission to research and develop some new anti-amyloid aggregation drugs. In recent years, there were research and development of engineered nanostructures as Aβ amyloid inhibitors have attracted extensive attention and become a new frontier in nanomedicine. The effects of nanostructural surface properties (e.g., morphology, charge, hydrophobicity) on inhibition of Aβ aggregation are modulated by adsorbed Aβ peptides. Nevertheless, chirality has been seldom considered in recognition of Aβ species and modulation of Aβ aggregations. Moreover, a more relevant question for chiral inhibitors is little known about the molecular mechanism of how to interface chiral effects Aβ targeting recognition and effective mitigation of amyloidosis at the molecular level. Herein, we review recent experimental and theoretical results acquired in the specific areas of artificial chiral nanostructure inhibitors. This article will be essential to provide a microlevel insight into the effects of chiral nanointerfaces on amyloidosis processes as well as the development of chiral inhibitor drugs against Aβ fibrillation.

Background Parkinson's disease is a common, progressive neurodegenerative disorder, the prevalence of which is on the rise. The diagnosis and management of Parkinson's disease is therefore likely to become increasingly frequent in general practice. Objective The aim of this article is to provide a practical overview for the general practitioner of the initial diagnosis and management of Parkinson's disease. Discussion Parkinson's disease is a multisystem disorder, and the way the diagnosis is delivered, as well as the early management, can have a lasting impact on the patient experience. In this article, the authors present their preferred approach to diagnosis and initial treatment, while highlighting common pitfalls and some useful simple strategies for communicating the diagnosis.

OBJECTIVE Parkinson's Disease (PD) is a progressive neurodegenerative disorder, manifesting with subtle early signs, which often hinder timely and early diagnosis and treatment. The development of accessible, technology-based methods for longitudinal PD symptoms tracking in daily living offers the potential for transforming the disease assessment and accelerating PD diagnosis. METHODS A privacy-aware method for classifying PD patients and healthy controls (HC), on the grounds of speech impairment present in PD, is proposed here. Voice features from running speech signals were extracted from recordings passively captured over voice phone calls. Features are fed in a language-aware training of multiple- and single-instance learning classifiers, along with demographic variables, exploiting a multilingual cohort of 498 subjects (392/106 self-reported HC/PD patients) to classify PD. RESULTS By means of leave-one-subject-out cross-validation, the best-performing models yielded 0.69/0.68/0.63/0.83 area under the Receiver Operating Characteristic curve (AUC) for the binary classification of PD patient vs. HC in sub-cohorts of English/Greek/German/Portuguese-speaking subjects, respectively. Out-of-sample testing of the best performing models was conducted in an additional dataset, generated by 63 clinically-assessed subjects (24/39 HC/early PD patients). Testing has resulted in 0.84/0.93/0.83 AUC for the English/Greek/German-speaking sub-cohorts, respectively. Comparative analysis with other approaches for language-aware PD detection justified the efficiency of the proposed one, considering the ecological validity of the acquired voice data. CONCLUSIONS The present work demonstrates increased robustness in PD detection using voice data captured in-the-wild. SIGNIFICANCE A high-frequency, privacy-aware and unobtrusive PD screening tool is introduced for the first time, based on analysis of voice samples captured during routine phone calls.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It can cause a massive impact on a patient's memory and mobility. As this disease is irreversible, early diagnosis is crucial for delaying the symptoms and adjusting the patient's lifestyle. Many machine learning (ML) and deep learning (DL) based approaches have been proposed to accurately predict AD before the onset of its symptoms. However, finding the most effective approach for AD early prediction is still challenging. This review explored 24 papers published from 2018 until 2021. These papers have proposed different approaches using state of the art machine learning and deep learning algorithms on different biomarkers to early detect AD. The review explored them from different perspectives to derive potential research gaps and draw conclusions and recommendations. It classified these recent approaches in terms of the learning technique used and AD biomarkers. It summarized and compared their findings, and defined their strengths and limitations. It also provided a summary of the common AD biomarkers. From this review, it was found that some approaches strove to increase the prediction accuracy regardless of their complexity such as using heterogeneous datasets, while others sought to find the most practical and affordable ways to predict the disease and yet achieve good accuracy such as using audio data. It was also noticed that DL based-approaches with image biomarkers remarkably surpassed ML based-approaches. However, they achieved poorly with genetic variants data. Despite the great importance of genetic variants biomarkers, their large variance and complexity could lead to a complex approach or poor accuracy. These data are crucial to discover the underlying structure of AD and detect it at early stages. However, an effective pre-processing approach is still needed to refine these data and employ them efficiently using the powerful DL algorithms.

Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder accompanied by behavioral and personality changes and/or language deterioration. Its behavioral variant (bvFTD) is the main clinical presentation. Objective: This study aims to investigate the treatment alternatives for bvFTD available so far. Methods: We conducted a narrative review of bvFTD treatment options. We used PubMed and Lilacs databases with the terms “frontotemporal dementia” or “behavioral variant frontotemporal dementia” combined with “treatment,” “pharmacological treatment,” or “disease-modifying drugs.” Results: The articles retrieved and selected in the research pointed out that there is no specific treatment approved for bvFTD so far. The current proposals are limited to handle the cardinal behavioral symptoms of the disorder. Disease-modifying drugs are under development and may be promising, especially in the monogenic presentations of FTD. Conclusions: There are numerous approaches to treat the core symptoms of bvFTD, most of them based on low-quality research. To date, there are no drugs with a disease-specific therapeutic recommendation for bvFTD. Treatments are often investigated guided by primary psychiatric disorders with similar symptoms and should be chosen by the predominant symptom profile. RESUMO A demência frontotemporal (DFT) é um transtorno neurodegenerativo progressivo acompanhado de deterioração do comportamento e da personalidade e/ou da linguagem. A variante comportamental (DFTvc) é a principal apresentação clínica. Objetivos: Investigar as alternativas de tratamento disponíveis para a DFTvc até o momento. Métodos: Realizou-se uma revisão narrativa das opções de tratamento da DFTvc. Os bancos de dados PubMed e Lilacs foram utilizados com os termos “demência frontotemporal” ou “variante comportamental da demência frontotemporal” combinados com “tratamento”, “tratamento farmacológico” ou “drogas modificadoras de doença”. Resultados: Os artigos recuperados e selecionados na pesquisa indicaram que não há nenhum tratamento específico aprovado até o momento para DFTvc. As propostas atuais são limitadas ao tratamento dos sintomas comportamentais cardinais do transtorno. As drogas modificadoras de doença estão em desenvolvimento e podem ser promissoras, especialmente nas apresentações monogênicas da DFT. Conclusões: Há inúmeras abordagens para tratar os principais sintomas DFTvc, a maioria delas baseada em pesquisas de baixa qualidade. Até o momento, não existem medicamentos com uma recomendação terapêutica específica para a DFTvc. Os tratamentos são frequentemente investigados guiados por distúrbios psiquiátricos primários com sintomas semelhantes e devem ser escolhidos pelo perfil de sintomas predominante.

Quinazolines are considered as a promising class of bioactive heterocyclic compounds with broad properties. Particularly, the quinazoline scaffold has an impressive role in the design and synthesis of new CNS-active drugs. The drug-like properties and pharmacological characteristics of quinazoline could lead to different drugs with various targets. Among CNS disorders, Alzheimer's disease (AD) is a progressive neurodegenerative disorder with memory loss, cognitive decline and language dysfunction. AD is a complex and multifactorial disease therefore, the need for finding multi-target drugs against this devastative disease is urgent. A literature survey revealed that quinazoline derivatives have diverse therapeutic potential for AD as modulators/inhibitors of β-amyloid, tau protein, cholinesterases, monoamine oxidases, and phosphodiesterases as well as other protective effects. Thus, we describe here the most relevant and recent studies about anti-AD agents with quinazoline structure which can further aid the development and discovery of new anti-AD agents.

Amyotrophic lateral sclerosis is a fatal, progressive neurodegenerative disorder characterized by motor neuron cell death in the brain and spinal cord. The typical disease symptom is the rapid loss of muscle control, which eventually leads to the complete paralysis of voluntary muscles of the entire body. There is no curative treatment for amyotrophic lateral sclerosis. The rarity of the disease and the difficulties in accurate early diagnosis are the major challenges in the proper understanding of the disease and the development of curative therapy. This book brings together a team of experts, both clinicians and basic scientists, to provide a comprehensive understanding of amyotrophic lateral sclerosis, challenges, and approaches to combat this devastating disease. The clinical chapters provide excellent views of diagnosis, pathology, management, and the problem of diagnostic delay. The basic science chapters provide a comprehensive description of pathomechanisms and therapies with emphasis on dysfunctional astrocytes, impaired synaptic transmission, defective axonal transport, biomarkers, cell-based therapies, and gut microbiota. The book is primarily aimed at clinicians and basic scientists; however, it will likely be of interest to a wide audience interested in amyotrophic lateral sclerosis.

BACKGROUND Huntington's disease (HD) is a progressive neurodegenerative disorder characterised by chorea, cognitive impairment, psychiatric and behavioral disturbances. Sleep disturbances including reduced REM sleep have been observed in HD. OBJECTIVES The aim of the study was to study the polysomnography findings in HD and to assess whether oculomotor abnormalities are associated with poor REM sleep. METHODS Twenty-nine genetically confirmed HD patients underwent clinical evaluation including extraocular movement and OKN examination. Twenty-six patients and 15 controls underwent overnight video polysomnography (VPSG). RESULTS VPSG of 23 HD patients and 13 controls were considered for analysis. Compared to controls, HD patients had higher median wake period and higher WASO percentage (p = 0.005). REM sleep percentage was reduced significantly in HD in comparison to controls (p

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization., This work was supported by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (Grant IJCI-2016-27658 to PMS, Grant PGC2018-094307-B-I00), the Cajal Blue Brain Project (the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland) and the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain). JBP is currently supported by Grants from the Swedish Research Council (#2018-02201), Hjärnfonden (#FO2019-0289), Alzheimerfonden (#AF-930827) and the Strategic Research Programme in Neuroscience at Karolinska Institutet (Stratneuro Startup Grant).

Parkinson’s disease is a progressive neurodegenerative disorder characterized by the death of nerve cells in the substantia nigra of the brain. The treatment options for this disease are very limited as currently the treatment is mainly symptomatic, and the available drugs are not able to completely stop the progression of the disease but only to slow it down. There is still a need to search for new compounds with the most optimal pharmacological profile that would stop the rapidly progressing disease. An increasing understanding of Parkinson’s pathogenesis and the discovery of new molecular targets pave the way to develop new therapeutic agents. The use and selection of appropriate cell and animal models that better reflect pathogenic changes in the brain is a key aspect of the research. In addition, computer-assisted drug design methods are a promising approach to developing effective compounds with potential therapeutic effects. In light of the above, in this review, we present current approaches for developing new drugs for Parkinson’s disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, resulting in the progressive decline of cognitive function in patients. Familial forms of AD are tied to mutations in the amyloid precursor protein, but the cellular mechanisms that cause AD remain unclear. Inflammation and amyloidosis from amyloid β (Aβ) aggregates are implicated in neuron loss and cognitive decline. Inflammation activates the protein-tyrosine phosphatase 1B (PTP1B), and this could suppress many signaling pathways that activate glycogen synthase kinase 3β (GSK3β) implicated in neurodegeneration. However, the significance of PTP1B in AD pathology remains unclear. Here, we show that pharmacological inhibition of PTP1B with trodusquemine or selective ablation of PTP1B in neurons prevents hippocampal neuron loss and spatial memory deficits in a transgenic AD mouse model with Aβ pathology (hAPP-J20 mice of both sexes). Intriguingly, while systemic inhibition of PTP1B reduced inflammation in the hippocampus, neuronal PTP1B ablation did not. These results dissociate inflammation from neuronal loss and cognitive decline and demonstrate that neuronal PTP1B hastens neurodegeneration and cognitive decline in this model of AD. The protective effect of PTP1B inhibition or ablation coincides with the restoration of GSK3β inhibition. Neuronal ablation of PTP1B did not affect cerebral amyloid levels or plaque numbers, but reduced Aβ plaque size in the hippocampus. In summary, our preclinical study suggests that targeting PTP1B may be a new strategy to intervene in the progression of AD. SIGNIFICANCE STATEMENT Familial forms of Alzheimer's disease (AD) are tied to mutations in the amyloid precursor protein, but the cellular mechanisms that cause AD remain unclear. Here, we used a mouse model expressing human amyloid precursor protein bearing two familial mutations and asked whether activation of a phosphatase PTP1B participates in the disease process. Systemic inhibition of this phosphatase using a selective inhibitor prevented cognitive decline, neuron loss in the hippocampus, and attenuated inflammation. Importantly, neuron-targeted ablation of PTP1B also prevented cognitive decline and neuron loss but did not reduce inflammation. Therefore, neuronal loss rather than inflammation was critical for AD progression in this mouse model, and that disease progression could be ameliorated by inhibition of PTP1B.

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder associated with expanded CAG repeat size in the huntingtin gene and usually presenting with movement disorder, psychiatric symptoms, and cognitive decline. Sleep problems, weight loss, and cachexia are also common. Here, we report a patient presenting with hypothermia in late-stage HD. Although thermoregulatory defects were documented in animal models, this is the first report describing HD with hypothermia in humans.

Celiac disease (CD) is an immune-mediated disease with varied intestinal and extraintestinal manifestations. Among extraintestinal manifestations, neurological conditions are being reported with increased frequency nowadays. We report a child of CD with progressively increasing dementia, poor scholastic performance, and myoclonic epilepsy. On further investigation, the cause of neurological manifestations was diagnosed as subacute sclerosing panencephalitis (SSPE). It is a slowly progressive neurodegenerative disorder caused by defective measles virus which is eventually fatal. The coexistence of CD and SSPE could not be found in literature.

Multiple system atrophy (MSA) is the most rapidly progressive neurodegenerative disorder among the various types of synucleinopathies. The cause of MSA remains unknown, but it can involve the extrapyramidal system, the pyramidal system, the autonomic nerves and the cerebellum. The main clinical manifestations are Parkinson's symptoms, cerebellar ataxia, pyramidal tract signs and autonomic nervous system disorders. Depending on the initial predominant motor deficits, MSA is subclassified into either Parkinsonian type (MSA-P) or cerebellar type (MSA-C). MSA is rare in the Zunyi area of Guizhou Province, so when it is observed for the first time it often results in a convoluted diagnosis and treatment process, which takes a lot of time, money, manpower and material resources, which can also have a psychological impact on the patient. This report describes the case of a 60-year-old woman who presented with syncope for 1 year combined with dizziness for 1 day. She had been diagnosed twice with transient ischaemic attack in the previous 6 months. Cranial magnetic resonance imaging suggested widening of the cerebellar sulcus and mild cerebellar atrophy. Based on the patient’s medical history, physical signs and auxiliary examinations, she was diagnosed with MSA-C.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder commonly observed in middle-aged and elderly. Currently, its etiology and pathogenesis are still not completely understood. It is associated with many symptoms that severely affect patients’ health and quality of life. At present, the PD clinical treatment mainly aimed to alleviate symptoms, and both medicinal and surgical treatments have side effects and treatment blind spots. The use of acupuncture for the treatment of PD is relatively widespread, and its safety and efficacy have been gradually accepted by the public and medical professions. However, the efficacy of acupuncture in experimental studies remains controversial. Therefore, this paper reviews imaging studies on the use of acupuncture for the treatment of PD. From the study, it shows that acupuncture can improve the neuronal activity, activate the neuronal activity in damaged brain regions, affect relevant neural networks and brain circulation, improve cerebral metabolism, and cause structural changes in related brain regions. Intuitive and visible imaging studies provide objective bases on the use of acupuncture for the treatment of PD.

Alzheimer's disease (AD) is a devastating slowly progressive neurodegenerative disorder with no cure. While there are many hypotheses, the exact mechanism causing this pathology is still unknown. Among many other features, AD is characterized by brain hypometabolism and decreased sugar availability, to which neurons eventually succumb. In light of this aspect of the disease, we hypothesized that boosting fuel supply to neurons may help them survive or at least alleviate some of the symptoms. Here we demonstrate that live moss Physcomitrella patens cells can be safely co-cultured with human fibroblasts in vitro and thus have a potential for providing human cells with energy and other vital biomolecules. These data may form the foundation for the development of novel approaches to metabolic bioengineering and treatment of diseased cells based on live plants. In addition, by providing alternative energy sources to human tissues, the biotechnological potential of this interkingdom setup could also serve as a springboard to foster innovative dietary processes addressing current challenges of mankind such as famine or supporting long-haul space flight.

BACKGROUND AND PURPOSE. Huntington disease (HD) is a progressive neurodegenerative disorder. There are no HD-specific measures to assess for end-of-life (EOL) preferences that have been validated for clinical use. The purpose of this study is to demonstrate reliability and validity of three HD-specific EOL measures for use in and clinical research settings. METHODS. We examined internal reliability, test-retest reliability, floor and ceiling effects, convergent and discriminant validity, known-groups validity, measurement error, and change over time to systematically examine reliability and validity of the HDQLIFE EOL measures. RESULTS. Internal consistency and test-retest reliability were >0.70. The measures were generally free of floor and ceiling effects and measurement error was minimal. Convergent and discriminant validity were consistent with well-known constructs in the field. Hypotheses for known groups validity were partially supported (there were generally group differences for the EOL Planning measures, but not for Meaning and Purpose or Concern with Death and Dying). Measurement error was acceptable and there were minimal changes over time across the EOL measures. CONCLUSIONS. Results support the clinical utility of the HDQLIFE EOL measures in persons with HD.

Amyloid beta (Aβ) oligomers are widely considered to be the causative agent of Alzheimer's disease (AD), a progressive neurodegenerative disorder. Determining the structure of oligomers is, therefore, important for understanding the disease and developing therapeutic agents; however, elucidating the structure has been proven difficult due to heterogeneity, noncrystallinity, and variability. Herein, we investigated homo- and hetero-oligomers of Aβ40 and Aβ42 using atomic force microscopy (AFM) and revealed characteristics of the molecular structure. By examining the surface of individual oligomers with sequential N- and C-terminus specific antibody-tethered tips, we simultaneously mapped the N- and C-terminus distributions and the elastic modulus. Interestingly, both the N- and C-termini of Aβ peptides were recognized on the oligomer surface, and the termini detected pixel regions exhibited a lower elastic modulus than silent pixel regions. These two types of regions were randomly distributed on the oligomer surface.

Chronic traumatic encephalopathy is a progressive neurodegenerative disorder that results from repetitive impacts to the head. Its distinguishing feature is an accumulation of abnormal tau proteins in characteristic regions within the brain. Histopathological studies reveal that tau consistently localizes at the depth of cerebral sulci; yet, the mechanistic origin of this pattern remains unclear. Here we show that a continuum damage model, enhanced with nonlocal gradients, can explain the initial distribution of abnormal tau proteins. We hypothesize that tau aggregation is associated with neuronal death, which we represent as tissue softening and stiffness degradation. Our simulations correctly identify the initial locations of tau deposition, at the depth of cerebral sulci, from where damage spreads within the cortical layer and then across the entire brain. Our computational model has the potential to provide a mechanistic explanation of the stereotypic histopathology of chronic traumatic encephalopathy and predict the cumulative effects of repeated mild traumatic brain injuries.