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Mitochondrial dysfunction and cognitive impairment are widespread phenomena among the elderly, being crucial factors that contribute to neurodegenerative diseases. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular defense systems, including that against oxidative stress. As such, increased Nrf2 activity may serve as a strategy to avert mitochondrial dysfunction and cognitive decline. Scientific data on Nrf2-mediated neuroprotection was collected from PubMed, Google Scholar, and Science Direct, specifically addressing mitochondrial dysfunction and cognitive impairment in older people. Search terms included "Nrf2", "mitochondrial dysfunction," "cognitive impairment," and "neuroprotection." Studies focusing on in vitro and in vivo models and clinical investigations were included to review Nrf2's therapeutic potential comprehensively. The relative studies have demonstrated that increased Nrf2 activity could improve mitochondrial performance, decrease oxidative pressure, and mitigate cognitive impairment. To a large extent, this is achieved through the modulation of critical cellular signalling pathways such as the Keap1/Nrf2 pathway, mitochondrial biogenesis, and neuroinflammatory responses. The present review summarizes the recent progress in comprehending the molecular mechanisms regarding the neuroprotective benefits mediated by Nrf2 through its substantial role against mitochondrial dysfunction and cognitive impairment. This review also emphasizes Nrf2-target pathways and their contribution to cognitive function improvement and rescue from mitochondria-related abnormalities as treatment strategies for neurodegenerative diseases that often affect elderly individuals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epilepsy, a neurological disorder characterized by prolonged and excessive seizures, has been linked to elevated levels of the tumor suppressor gene p53, which contributes to neuronal dysfunction. This review explores the molecular mechanisms of p53 in epilepsy and discusses potential future therapeutic strategies. Research indicates that changes in p53 expression during neuronal apoptosis, neuroinflammation, and oxidative stress play a significant role in the pathogenesis of epilepsy. Elevated p53 disrupts glutamatergic neurotransmission and hyperactivates NMDA and AMPA receptors, leading to increased neuronal calcium influx, mitochondrial oxidative stress, and activation of apoptotic pathways mediated neuronal dysfunction, exacerbating epileptogenesis. The involvement of p53 in epilepsy suggests that targeting this protein could be beneficial in mitigating neuronal damage and preventing seizure recurrence. Pharmacological agents like pifithrin-α have shown promise in reducing p53-mediated apoptosis and seizure severity. Gene therapy approaches, such as viral vector-mediated delivery of wild-type p53 or RNA interference targeting mutant p53, have also been effective in restoring normal p53 function and reducing seizure susceptibility. Despite these advances, the heterogeneous nature of epilepsy and potential long-term side effects of p53 modulation present challenges. Future research should focus on elucidating the precise molecular mechanisms of p53 and developing personalized therapeutic strategies. Modulating p53 activity holds promise for reducing seizure susceptibility and improving the quality of life for individuals with epilepsy. The current review provides the understanding the intricate role of p53 in neuroinflammatory pathways, including JAK-STAT, JNK, NF-κB, Sonic Hedgehog, and Wnt, is crucial for developing targeted therapies., Competing Interests: Declaration of competing interest This is to bring to your kind notice that the manuscript originally written by Vrinda Gupta, Shareen Singh, Thakur Gurjeet Singh titled “Pervasive Expostulation of p53 Gene Promoting the Precipitation of Neurogenic Convulsions: A Journey in Therapeutic Advancements” is here with submitted for publication in European Journal of Pharmacology. It has not been published before, and it is not under consideration for publication in any other journal (s).We certify that we have obtained written permission for the use of text, tables, and/or illustrations from any copyrighted source(s), and we declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The coexistence of cancer and heart disease, both prominent causes of illness and death, is further exacerbated by the detrimental impact of chemotherapy. Anthracycline-induced cardiotoxicity is an unfortunate side effect of highly effective therapy in treating different types of cancer; it presents a significant challenge for both clinicians and patients due to the considerable risk of cardiotoxicity. Despite significant progress in understanding these mechanisms, challenges persist in identifying effective preventive and therapeutic strategies, rendering it a subject of continued research even after three decades of intensive global investigation. The molecular targets and signaling pathways explored provide insights for developing targeted therapies, emphasizing the need for continued research to bridge the gap between preclinical understanding and clinical applications. This review provides a comprehensive exploration of the intricate mechanisms underlying anthracycline-induced cardiotoxicity, elucidating the interplay of various signaling pathways leading to adverse cellular events, including cardiotoxicity and death. It highlights the extensive involvement of pathways associated with oxidative stress, inflammation, apoptosis, and cellular stress responses, offering insights into potential and unexplored targets for therapeutic intervention in mitigating anthracycline-induced cardiac complications. A comprehensive understanding of the interplay between anthracyclines and these complexes signaling pathways is crucial for developing strategies to prevent or mitigate the associated cardiotoxicity. Further research is needed to outline the specific contributions of these pathways and identify potential therapeutic targets to improve the safety and efficacy of anthracycline-based cancer treatment. Ultimately, advancements in understanding anthracycline-induced cardiotoxicity mechanisms will facilitate the development of more efficacious preventive and treatment approaches, thereby improving outcomes for cancer patients undergoing anthracycline-based chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a complex, multiple etiology that is marked by impaired social interaction, communication, and repetitive behaviour. There is presently no pharmaceutical treatment for the core symptoms of ASD, even though the prevalence of ASD is increasing worldwide. Treatment of autism spectrum disorder involves the interaction of numerous signalling pathways, such as the Wnt/beta-catenin pathway, probiotics and kynurenine pathway, PPAR pathway, PI3K-AKT-mTOR pathway, Hedgehog signaling pathway, etc. The scientific literature has revealed TWEAK/Fn14 to not be explored in the autism spectrum disorder. In vitro and in vivo, TWEAK can control a wide range of cellular responses. Recent research has revealed that TWEAK and Fn14 are expressed in the Central Nervous System (CNS) and upregulated in perivascular endothelial cells, astrocytes, neurons, and microglia in response to various stimuli, including cerebral ischemia. This upregulation is followed by cell death and an increase in Blood-brain Barrier (BBB) permeability. The study has revealed that Aurintricarboxylic Acid (ATA) acts as an agent that suppresses TWEAK/Fn14 signaling. Similarly, from the discussion, it has been emphasized that the proposed molecular TWEAK/Fn14 signalling pathway can be considered as a therapeutic approach in the management of autism spectrum disorder., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease is an ailment that is linked with the degeneration of the brain cells, and this illness is the main cause of dementia. Metabolic stress affects the activity of the brain in AD via FOXO signaling. The occurrence of AD will significantly surge as the world's population ages, along with lifestyle changes perceived in current decades, indicating a main contributor to such augmented prevalence. Similarly, metabolic disorders of current adulthood, such as obesity, stroke, and diabetes mellitus, have been observed as the risk-causing factors of AD. Environmental influences induce genetic mutations that result in the development of several diseases. Metabolic disorders develop when individuals are exposed to an environment where food is easily accessible and requires minimal energy expenditure. Obesity and diabetes are among the most significant worldwide health concerns. Obesity arises because of an imbalance between the amount of energy consumed and the amount of energy expended, which is caused by both behavioral and physiological factors. Obesity, insulin resistance syndrome, hypertension, and inflammation are factors that contribute to the worldwide risk of developing diabetes mellitus and neurodegenerative diseases. FOXO transcription factors are preserved molecules that play an important part in assorted biological progressions, precisely in aging as well as metabolism. Apoptosis, cell division and differentiation, oxidative stress, metabolism, and lifespan are among the physiological processes that the FOXO proteins are adept at controlling. In this review, we explored the correlation between signaling pathways and the cellular functions of FOXO proteins. We have also summarized the intricate role of FOXO in AD, with a focus on metabolic stress, and discussed the prospect of FOXO as a molecular link between AD and metabolic disorders., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Ischemic injury to the brain can result in a variety of life-threatening conditions, mortality, or varying degrees of disability. Hypoxia-inducible factor 1α (HIF 1α), an oxygen- sensitive transcription factor that controls the adaptive metabolic response to hypoxia, is a critical constituent of cerebral ischemia. It participates in numerous processes, such as metabolism, proliferation, and angiogenesis, and plays a major role in cerebral ischemia., Methods: Through the use of a number of different search engines like Scopus, PubMed, Bentham, and Elsevier databases, a literature review was carried out for investigating the pharmacological modulation of HIF-1α pathways for the treatment of cerebral ischemia., Results: Various signalling pathways, such as Mitogen-activated protein kinase (MAPK), Janus kinase/ signal transducers and activators (JAK/STAT), Phosphoinositide-3-kinase (PI3-K), and cAMPresponse element binding protein (CREB) play a vital role in modulation of HIF-1α pathway, which helps in preventing the pathogenesis of cerebral ischemia., Conclusion: The pharmacological modulation of the HIF-1α pathway via various molecular signalling pathways, such as PI3-K, MAPK, CREB, and JAK/STAT activators, offer a promising prospect for future interventions and treatment for cerebral ischemia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sirtuin 1 (SIRT1), an NAD+-dependent deacetylase, has emerged as a key regulator of cellular processes linked to ageing and neurodegeneration. SIRT1 modulates various signalling pathways, including those involved in autophagy, oxidative stress, and mitochondrial function, which are critical in the pathogenesis of neurodegenerative diseases. This review explores the therapeutic potential of SIRT1 in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Preclinical studies have demonstrated that SIRT1 activators, such as resveratrol, SRT1720, and SRT2104, can alleviate disease symptoms by reducing oxidative stress, enhancing autophagic flux, and promoting neuronal survival. Ongoing clinical trials are evaluating the efficacy of these SIRT1 activators, providing hope for future therapeutic strategies targeting SIRT1 in neurodegenerative diseases. This review explores the role of SIRT1 in ageing and neurodegenerative diseases, with a particular focus on its molecular mechanisms, therapeutic potential, and clinical applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Diabetic wounds are often chronic in nature, and issues like elevated blood sugar, bacterial infections, oxidative stress and persistent inflammation impede the healing process. To ensure the appropriate healing of wounds, scaffolds should promote complete tissue regeneration in wounds, both functionally and structurally. However, the available scaffolds lack the explicit architecture and functionality that could match those of native skin, thus failing to carry out the scar-free skin regeneration in diabetic wounds. This study deals with the synthesis of a bi-layered nanofibrous scaffold mimicking the native skin architecture in terms of porosity and hydrophobic-hydrophilic gradients. In addition, herbal extracts of Aloe vera and litchi honey were added in consecutive layers to manage the high blood glucose level, inflammation, and increased ROS level associated with diabetic wounds. In vitro studies confirmed that the prepared scaffold with herbal extracts showed enhanced proliferation of skin cells with good mechanical strength, degradability, anti-bacterial and anti-diabetic properties. The scaffold also demonstrated superior wound healing in vivo with quicker scar-free wound recovery and appropriate skin regeneration, compared to conventional treatment. Altogether, the synthesized herbal extract loaded bi-layered nanofibrous scaffold can be used as a regenerative template for hard-to-heal diabetic wounds, offering a new strategy for the management of chronic wounds.

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder affecting individuals worldwide. It is characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. The pathogenesis of HD involves oxidative stress, neuroinflammation, and mitochondrial dysfunction. Nuclear factor erythroid 2-related factor 2 (Nrf2), a key transcription factor regulating cellular responses to redox imbalance and inflammation, has emerged as a potential target for therapeutic intervention., Methods: Through the use of a number of different search engines like Scopus, PubMed, Elsevier and Bentham, a literature review was carried out with the keywords 'Huntington's Disease, 'Pathology of HD' and 'Nrf2 signalling pathway'. Using the keywords that were given above, this review was carried out in order to collect the most recent publications and gain an understanding of the breadth of the extensive research that has been conducted on the role of Nrf2 in HD pathogenesis., Results: Oxidative stress and neuroinflammation significantly contribute to HD progression. Activation of Nrf2 offers neuroprotection by enhancing anti-oxidant defense mechanisms. Furthermore, several signaling pathways, play crucial roles in HD pathophysiology. Pharmacological modulation of these pathways through selective inhibitors or agonists shows promise for the development of new therapeutic strategies., Conclusion: The various downstream pathways such as extracellular signal-related kinase (ERK), phosphoinositide 3-Kinase (PI3-K), 5'-AMP-activated protein kinase (AMPK), Sirtuins, Mitogen-activated protein kinases (MAPK) plays a role in alleviating pathophysiology of HD. Diverse reports of these studies demonstrated PI3-K/AMPK/ERK/Sirtuins activators and MAPK inhibitors as encouraging targets in alleviating HD pathophysiology., (© 2024. Fondazione Società Italiana di Neurologia.)

Cerebral ischemic injury is characterized by reduced blood flow to the brain, remains a significant cause of morbidity and mortality worldwide. Despite improvements in therapeutic approaches, there is an urgent need to identify new targets to lessen the effects of ischemic stroke. Aquaporins, a family of water channel proteins, have recently come to light as promising candidates for therapeutic intervention in cerebral ischemic injury. There are 13 aquaporins identified, and AQP4 has been thoroughly involved with cerebral ischemia as it has been reported that modulation of AQP4 activity can offers a possible pathway for therapeutic intervention along with their role in pH, osmosis, ions, and the blood-brain barrier (BBB) as possible therapeutic targets for cerebral ischemia injury. The molecular pathways which can interacts with particular cellular pathways, participation in neuroinflammation, and possible interaction with additional proteins thought to be involved in the etiology of a stroke. Understanding these pathways offers crucial information on the diverse role of AQPs in cerebral ischemia, paving the door for the development of focused/targeted therapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Huntington's disease (HD) is a devastating neurodegenerative disease that is manifested by a gradual loss of physical, cognitive, and mental abilities. As the disease advances, age has a major impact on the pathogenic signature of mutant huntingtin (mHTT) protein aggregation. This review aims to explore the intricate relationship between aging, mHTT toxicity, and cellular senescence in HD. Scientific data on the interplay between aging, mHTT, and cellular senescence in HD were collected from several academic databases, including PubMed, Google Scholar, Google, and ScienceDirect. The search terms employed were "AGING," "HUNTINGTON'S DISEASE," "MUTANT HUNTINGTIN," and "CELLULAR SENESCENCE." Additionally, to gather information on the molecular mechanisms and potential therapeutic targets, the search was extended to include relevant terms such as "DNA DAMAGE," "OXIDATIVE STRESS," and "AUTOPHAGY." According to research, aging leads to worsening HD pathophysiology through some processes. As a result of the mHTT accumulation, cellular senescence is promoted, which causes DNA damage, oxidative stress, decreased autophagy, and increased inflammatory responses. Pro-inflammatory cytokines and other substances are released by senescent cells, which may worsen the neuronal damage and the course of the disease. It has been shown that treatments directed at these pathways reduce some of the HD symptoms and enhance longevity in experimental animals, pointing to a new possibility of treating the condition. Through their amplification of the harmful effects of mHTT, aging and cellular senescence play crucial roles in the development of HD. Comprehending these interplays creates novel opportunities for therapeutic measures targeted at alleviating cellular aging and enhancing HD patients' quality of life., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

The persistent use of opioids leads to profound changes in neuroplasticity of the brain, contributing to the emergence and persistence of addiction. However, chronic opioid use disrupts the delicate balance of the reward system in the brain, leading to neuroadaptations that underlie addiction. Chronic cocaine usage leads to synchronized alterations in gene expression, causing modifications in the Nucleus Accumbens (NAc), a vital part of the reward system of the brain. These modifications assist in the development of maladaptive behaviors that resemble addiction. Neuroplasticity in the context of addiction involves changes in synaptic connectivity, neuronal morphology, and molecular signaling pathways. Drug-evoked neuroplasticity in opioid addiction and withdrawal represents a complicated interaction between environmental, genetic, and epigenetic factors. Identifying specific transcriptional and epigenetic targets that can be modulated to restore normal neuroplasticity without disrupting essential physiological processes is a critical consideration. The discussion in this article focuses on the transcriptional aspects of drug-evoked neuroplasticity, emphasizing the role of key transcription factors, including cAMP response element-binding protein (CREB), ΔFosB, NF-kB, Myocyte-enhancing factor 2 (MEF2), Methyl-CpG binding protein 2 (MeCP2), E2F3a, and FOXO3a. These factors regulate gene expression and lead to the neuroadaptive changes observed in addiction and withdrawal. Epigenetic regulation, which involves modifying gene accessibility by controlling these structures, has been identified as a critical component of addiction development. By unraveling these complex molecular processes, this study provides valuable insights that may pave the way for future therapeutic interventions targeting the mechanisms underlying addiction and withdrawal., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on μ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin-angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Nrf2, a crucial protein involved in defense mechanisms, particularly oxidative stress, plays a significant role in neurological diseases (NDs) by reducing oxidative stress and inflammation. NDs, including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, stroke, epilepsy, schizophrenia, depression, and autism, exhibit ferroptosis, iron-dependent regulated cell death resulting from lipid and iron-dependent reactive oxygen species (ROS) accumulation. Nrf2 has been shown to play a critical role in regulating ferroptosis in NDs. Age-related decline in Nrf2 expression and its target genes (HO-1, Nqo-1, and Trx) coincides with increased iron-mediated cell death, leading to ND onset. The modulation of iron-dependent cell death and ferroptosis by Nrf2 through various cellular and molecular mechanisms offers a potential therapeutic pathway for understanding the pathological processes underlying these NDs. This review emphasizes the mechanistic role of Nrf2 and ferroptosis in multiple NDs, providing valuable insights for future research and therapeutic approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer remains one of the predominant causes of mortality globally, accounting for over 10 million deaths each year. Despite advancements in medical treatments, the challenge of resistance and treatment failure persists, necessitating innovative approaches. Traditional cancer treatments include surgery, chemotherapy, radiation therapy, and pharmaceutical therapy. In recent years, significant attention has been directed towards plant-derived compounds as potential chemotherapeutic agents and preventive measures against cancer. Vincristine, a distinguished alkaloid derived from plant secondary metabolites, has shown considerable efficacy in cancer treatment. As a member of the antimitotic class of compounds, vincristine disrupts the cell cycle by causing aberrations in microtubule function, thereby inhibiting cell division and proliferation. This mechanism of action positions vincristine as a potent agent against various malignancies. Its role in combination therapy is crucial, as it is often administered in low doses alongside other chemotherapeutic agents to enhance its efficacy and reduce the risk of resistance. In the realm of medicinal chemistry, understanding vincristine's molecular mechanism is paramount. Detailed investigations into its interaction with cellular components can provide insights into its antineoplastic properties. This review aimed to elucidate vincristine's mechanism of action and structure-activity relationship, and summarize current in vitro and in vivo studies evaluating its efficacy. Moreover, it discusses innovative strategies, including nanotechnology-based delivery systems, designed to optimize vincristine formulations. These advanced delivery systems aim to improve bioavailability, target specificity, and minimize systemic toxicity. This comprehensive analysis underscores the critical role of vincristine in contemporary cancer treatment and highlights future directions for research and development in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease is a neurodegenerative problem with progressive loss of memory and other cognitive function disorders resulting in the imbalance of neurotransmitter activity and signaling progression, which poses the need of the potential therapeutic target to improve the intracellular signaling cascade brought by kinases. Protein kinase plays a significant and multifaceted role in the treatment of Alzheimer's disease, by targeting pathological mechanisms like tau hyperphosphorylation, neuroinflammation, amyloid-beta production and synaptic dysfunction. In this review, we thoroughly explore the essential protein kinases involved in Alzheimer's disease, detailing their physiological roles, regulatory impacts, and the newest inhibitors and compounds that are progressing into clinical trials. All the findings of studies exhibited the promising role of kinase inhibitors in the management of Alzheimer's disease. However, it still poses the need of addressing current challenges and opportunities involved with this disorder for the future perspective of kinase inhibitors in the management of Alzheimer's disease. Further study includes the development of biomarkers, combination therapy, and next-generation kinase inhibitors with increased potency and selectivity for its future prospects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Ischemia-reperfusion (I/R) injury refers to the tissue damage that happens when blood flow returns to tissue after a period of ischemia. I/R injuries are implicated in a large array of pathological conditions, such as cerebral, myocardial, renal, intestinal, retinal and hepatic ischemia. The hallmark of these pathologies is excessive inflammation. Toll-like receptors (TLRs) are recognized as significant contributors to inflammation caused by pathogens and, more recently, inflammation caused by injury. TLR-4 activation initiates a series of events that results in activation of nuclear factor kappa-B (NF-κB), which stimulates the production of pro-inflammatory cytokines and chemokines, exacerbating tissue injury. Therefore, through a comprehensive review of current research and experimentation, this investigation elucidates the TLRs signalling pathway and the role of TLR-4/NF-κB in the pathophysiology of I/R injuries. Furthermore, this review highlights the various pharmacological agents (TLR-4/NF-κB inhibitors) with special emphasis on the various ischemic injuries (cerebral, myocardial, renal, intestinal, retinal and hepatic). Future research should prioritise investigating the specific molecular pathways that cause TLR-4/NF-κBmediated inflammation in ischemic injuries. Additionally, efforts should be made to enhance treatment approaches in order to enhance patient outcomes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multiple sclerosis (MS) is an unceasing, demyelinating, idiopathic inflammatory, and neurodegenerative disease of the Central Nervous System (CNS.) The disease is characterized by the occurrence of neurological symptoms over a period of days to weeks, abide by partial or absolute diminutions of various durations. In this review, a concise outline on disease activity and progression of MS, pathogenesis with the special prominence on the biomarkers for the MS as therapeutic targets has been discussed by carrying out a comprehensive literature survey employing chief websites and search engines for investigation. Cortical inflammation, neurodegeneration, demyelination, axonal injury, axonal loss, oligodendrocytes, mitochondrial dysfunction, microglia activation, oxidative and nitrosative stress are the pathological hallmarks of the MS. CNS neurofilaments, chitinase and chitinase 3-like proteins, soluble circulating form (sCD163), Chemokine ligand 13 (CXCL13), immunoglobulin M, MicroRNA (miRNA) and messenger Ribonucleic Acid (mRNA), Glial fibrillary acidic protein (GFAP), serum osteopontin, 8-iso-prostaglandin F2α (8-iso-PGF2 α), apo-Lipoprotein E and myelinreactive T cells are some of the therapeutically valuable biomarkers for such multifarious disorder. MS is one of the chronic neurodegenerative diseases with undefined etiology. The study of the pathophysiology of the disease and the involvement of certain biomarkers can help identify new targets for therapeutic intercession, identify individuals at risk of developing the disease later in life, and allow more effective treatment of progressive diseases such as MS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Psychiatric disorders such as Bipolar disorder, Anxiety, Major depressive disorder, Schizophrenia, Attention-deficit/hyperactivity disorder, as well as neurological disorders such as Migraine, are linked by the evidence of altered calcium homeostasis. The disturbance of intra-cellular calcium homeostasis disrupts the activity of numerous ion channels including transient receptor potential (TRP) channels. TRP channel families comprise non-selective calcium-permeable channels that have been implicated in variety of physiological processes in the brain, as well as in the pathogenesis of psychiatric disorders. Through a comprehensive review of current research and experimentation, this investigation elucidates the role of TRP channels in psychiatric disorders. Furthermore, this review discusses about the exploration of epigenetics and TRP channels in psychiatric disorders., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Pyroptosis is an inflammatory programed cell death process that plays a crucial role in cancer therapeutic, while Gasdermin-D is a critical effector protein for pyroptosis execution. This review discusses the intricate interactions between Gasdermin-D and some non-coding RNAs (lncRNA, miRNA, siRNA) and their potential application in the regulation of pyroptosis as an anticancer therapy. Correspondingly, these ncRNAs significantly implicate in Gasdermin-D expression and function regarding the pyroptosis pathway. Functioning as competing endogenous RNAs (ceRNAs), these ncRNAs might regulate Gasdermin-D at the molecular level, underlying fatal cell death caused by cancer and tumor propagation. Therefore, these interactions appeal to therapeutics, offering new avenues for cancer treatment. It address this research gap by discussing the possible roles of ncRNAs as mediators of gasdermin-D regulation. It suggest therapeutic strategies based on the current research findings to ensure the interchange between the ideal pyroptosis and cancer cell death., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: Although real-world studies demonstrate that those prescribed nirmatrelvir/ritonavir (and particularly within 5 days of symptom onset) are less likely to experience severe COVID-19 outcomes, prior studies show that only a small fraction of patients with COVID-19 who are eligible for nirmatrelvir/ritonavir receive a prescription. Studies calculating the proportion of nirmatrelvir/ritonavir prescriptions filled and identifying individual- and pharmacy-level correlates of filling nirmatrelvir/ritonavir are lacking., Methods: This retrospective cohort study included individuals aged ≥ 12 years with a nirmatrelvir/ritonavir prescription ordered at a large national retail pharmacy (December 22, 2021-August 12, 2023). Those taking contraindicated medications were excluded. For those with only one nirmatrelvir/ritonavir prescription ordered, the outcome was whether the prescription was filled (yes/no). In a subanalysis of these individuals, the outcome was whether the prescription was filled within 5 days of symptom onset (yes/no). For those with multiple prescriptions ordered, the outcome was whether > 1 (vs. 0 or 1) prescriptions were filled. A log-binomial regression with generalized estimating equations was used to identify individual (clinical and demographic) and pharmacy-level (percentage of trade area that is non-Hispanic white, urbanicity, US Census region, and tract-level area deprivation index) correlates., Results: A total of 2,103,570 unique nirmatrelvir/ritonavir prescriptions were ordered for 1,985,990 individuals. Among the 95% of individuals prescribed only one nirmatrelvir/ritonavir course, 88% filled their prescription. Among those with > 1 prescription ordered, 77% (82,993/108,411) filled one and 13% (13,662/108,411) filled > 1. Patients ≥ 50 years of age and those with documented high-risk conditions were slightly more likely to fill prescriptions, regardless of whether one or multiple courses were ordered. Individuals with cancer, asthma, or taking corticosteroids or immunosuppressive medications were more likely to fill multiple prescriptions., Conclusions: Most patients filled their nirmatrelvir/ritonavir prescriptions. Interventions to improve uptake should focus on increasing patient and provider awareness, reducing nirmatrelvir/ritonavir prescribing disparities, and ensuring treatment initiation within 5 days., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative primarily affecting motor neurons, leading to disability and neuronal death, and ATP-Binding Cassette (ABC) transporter due to their role in drug efflux and modulation of various cellular pathways contributes to the pathogenesis of ALS. In this article, we extensively investigated various molecular and mechanistic pathways linking ALS transporter to the pathogenesis of ALS; this involves inflammatory pathways such as Mitogen-Activated Protein Kinase (MAPK), Phosphatidylinositol-3-Kinase/Protein Kinase B (PI3K/Akt), Toll-Like Receptor (TLR), Glycogen Synthase Kinase 3β (GSK-3β), Nuclear Factor Kappa-B (NF-κB), and Cyclooxygenase (COX). Oxidative pathways such as Astrocytes, Glutamate, Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin 1 (SIRT-1), Forkhead box protein O (FOXO), Extracellular signal-regulated kinase (ERK). Additionally, we delve into the role of autophagic pathways like TAR DNA-binding protein 43 (TDP-43), AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and lastly, the apoptotic pathways. Furthermore, by understanding these intricate interactions, we aim to develop novel therapeutic strategies targeting ABC transporters, improving drug delivery, and ultimately offering a promising avenue for treating ALS., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The ions Ca 2+ and Mg 2+ , which are both present in the body, have been demonstrated to be crucial in the control of a variety of neuronal processes. Transient melastatin-7 (TRPM7) channel plays an important role in controlling Ca 2+ and Mg 2+ homeostasis, which is crucial for biological processes. The review will also examine how changes in TRPM7 function or expression can lead to neurodegeneration.Even though eight different TRPM channels have been found so far, the channel properties, activation mechanisms, and physiological responses exhibited by these channels can vary greatly from one another. Only TRPM6 and TRPM7 out of the eight TRPM channels were found to have a high permeability to both Ca 2+ and Mg 2+ . In contrast to TRPM6 channels, which are not highly expressed in neuronal cells, TRPM7 channels are widely distributed throughout the nervous system, so they will be the sole focus of this article. It is possible that, in the future, for the treatment of neurodegenerative disorder new therapeutic drug targets will be developed as a direct result of research into the specific roles played by TRPM7 channels in several different neurodegenerative conditions as well as the factors that are responsible for TRPM7 channel regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Leukotrienes (LTs) are a group of substances that cause inflammation. They are produced by the enzyme 5-lipoxygenase (5-LOX) from arachidonic acid. Cysteinyl LTs are a group of lipid molecules that have a prominent role in inflammatory signaling in the allergic diseases. Although they are traditionally known for their role in allergic disease, current advancements in bio-medical research have shed light on the involvement of these inflammatory mediators in diseases such as in the inflammation related to central nervous system (CNS) disorders. Among the CNS diseases, LTs, along with 5-LOX and their receptors, have been shown to be associated with multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD). Through a comprehensive review of current research and experimentation, this investigation provides an insight on the biosynthesis, receptors, and biological effects of LTs in the body. Furthermore, implications of leukotriene signaling in CNS and its intricate role in neurodegeneration are also studied. Through the revelation of these insights, our aim is to establish a foundation for the development of enhanced and focused therapeutic approaches in the continuous endeavor to combat neurodegeneration. Furthermore, the pharmacological inhibition of leukotriene signaling with selective inhibitors offers promising prospects for future interventions and treatments for neurodegenerative diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)