AIMS Neuroscience最新文献

{"title":"Glial-Dopamine crosstalk: Astrocytic and microglial gatekeepers of neuroinflammation, plasticity, and motivation.","authors":"Moawiah M Naffaa","doi":"10.3934/Neuroscience.2026004","DOIUrl":"10.3934/Neuroscience.2026004","url":null,"abstract":"<p><p>Dpamine (DA) signaling has long been framed through a neuron-centric lens; yet, mounting evidence reveals that glial cells (astrocytes and microglia) serve as indispensable gatekeepers of dopaminergic tone, synaptic plasticity, and neuroimmune balance. Single-cell, spatial, and optical imaging studies have redefined DA circuits as multicellular ecosystems in which glial receptors, transporters, and gliotransmitters dynamically sculpt neuromodulation and behavior. Astrocytes fine-tune DA clearance, glutamate buffering, and metabolic coupling, while microglia integrate immune and stress cues recalibrate dopaminergic signaling across striatal and cortical circuits. Their bidirectional interactions, both glia-glia and glia-neuron, mediate resilience or vulnerability in contexts ranging from motivation and stress adaptation to Parkinson's disease (PD), depression, and post-viral fatigue syndromes. In this review, we synthesized emerging evidence that glial-DA crosstalk is a systems-level regulator of neuroinflammation and plasticity, bridging cellular metabolism, immune tone, and behavioral output. By integrating multi-omics, in vivo imaging, and computational models, we proposed a translational framework for targeting astrocytic and microglial states to restore dopaminergic homeostasis. Understanding and manipulating these non-neuronal interfaces may open the next frontier in precision neuropsychiatry and neurodegeneration therapeutics.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"13 1","pages":"64-118"},"PeriodicalIF":4.3,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of repetitive transcranial magnetic stimulation modulating supplementary motor area in stroke rehabilitation: Systematic review of randomized controlled trials.","authors":"Ayesha Juhi, Shreya Sharma, Dinesh Bhatia, Suman Dhaka, Rajesh Kumar, Deepak Kumar, Rintu Kumar Gayen, Himel Mondal","doi":"10.3934/Neuroscience.2026003","DOIUrl":"10.3934/Neuroscience.2026003","url":null,"abstract":"<p><strong>Background: </strong>Repetitive transcranial magnetic stimulation (rTMS) is a promising adjunct in stroke rehabilitation, with increasing focus on the supplementary motor area (SMA) for its role in motor and language network reorganization. This systematic review evaluated randomized controlled trials (RCTs) assessing rTMS targeting the SMA or modulating its connectivity to improve motor and language outcomes in adults after ischemic or hemorrhagic stroke.</p><p><strong>Methods: </strong>A comprehensive literature search was performed across PubMed, Web of Science, and Google Scholar, focusing on peer-reviewed RCTs published in English. Studies were eligible if they involved adults with stroke at any recovery stage and assessed rTMS targeting or analyzing the SMA. Two independent reviewers screened records, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2.0 tool. The review adhered to PRISMA guidelines and was registered in PROSPERO (CRD420251051684).</p><p><strong>Results: </strong>Among 74 screened for full text, five RCTs were included. Across studies, rTMS interventions targeting the SMA or modulating SMA-related networks improved motor and language outcomes in stroke patients. Neuroimaging measures consistently demonstrated increased SMA activation and strengthened SMA-primary motor cortex (M1) connectivity after rTMS, which correlated with clinical improvements. Balance and postural control outcomes showed the most consistent benefits, while upper-limb motor and language improvements varied in magnitude and follow-up duration.</p><p><strong>Conclusion: </strong>Heterogeneity in studies, small sample sizes, and concerns about randomization and reporting limit our ability to draw definitive conclusions. SMA-targeted or network-level rTMS appears to facilitate functional recovery after stroke, supported by neuroimaging evidence of brain network reorganization. Further large, standardized RCTs are necessary to establish optimal protocols, confirm efficacy, and assess long-term outcomes.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"13 1","pages":"50-63"},"PeriodicalIF":4.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal 4-phenylbutyric acid administration during mid-gestation ameliorates ASD-like behaviors by reducing cortical endoplasmic reticulum stress in VPA-induced ICR and BTBR mouse models.","authors":"Koichi Kawada, Seisuke Mimori, Nobuyuki Kuramoto, Kyosuke Uno","doi":"10.3934/Neuroscience.2026002","DOIUrl":"10.3934/Neuroscience.2026002","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and repetitive behaviors. Increasing evidence suggests that endoplasmic reticulum (ER) stress contributes to abnormal brain development in ASD; however, whether prenatal modulation of ER stress can prevent ASD-like phenotypes remains unclear. In this study, we investigated the effects of prenatal administration of the chemical chaperone 4-phenylbutyric acid (4-PBA) in two etiologically distinct ASD mouse models: valproic acid (VPA)-exposed Jcl:ICR (ICR) mice and BTBR <i>T⁺ Itpr3^tf</i> /J (BTBR) mice. Social behaviors were evaluated using the three-chamber test, and repetitive behaviors were assessed by self-grooming duration. 4-PBA was administered to mid-gestation mice, and behavioral changes in the male offspring derived-two type ASD model (VPA and BTBR mice) were evaluated. 4-PBA reduced ER stress in the cerebral cortex of the offspring male VPA and BTBR mice. In particular, 4-PBA strongly inhibited the expression of 94-kDa glucose-regulated protein, an ER stress marker, in BTBR male mice. In addition, 4-PBA improved synaptic organizer expression and neuronal maturation, which are diminished in ASD, specifically in the cerebral cortex of VPA mice. Furthermore, 4-PBA improved social reciprocity, a behavior specific to ASD in male VPA and BTBR mice. In conclusion, ER stress during mid-pregnancy is strongly associated with the development of ASD symptoms. Furthermore, the reduction in ER stress by 4-PBA leads to the suppression of ASD symptoms. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by a lack of sociality, and the difficulty in forming social relationships often leads to various social problems. Prenatal administration of 4-PBA to mothers may reduce the risk of developing ASD, and we believe this could be a new approach to prevention.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"13 1","pages":"29-49"},"PeriodicalIF":4.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stingless bee honey alleviates cognitive deficits and hippocampal neurodegeneration in an Alzheimer's model: Behavioural, neurochemical, and histological analyses.","authors":"Shah Rezlan Shajahan, Zaw Myo Hein, Hussin Muhammad, Mohd Zulkifli Mustafa, Yatinesh Kumari, Imrana Jazuli, Azlina Zulkapli, Norshafarina Shari, Che Mohd Nasril Che Mohd Nassir, Muhammad Danial Che Ramli","doi":"10.3934/Neuroscience.2026001","DOIUrl":"10.3934/Neuroscience.2026001","url":null,"abstract":"<p><p>Stingless bee honey (SBH), widely consumed in Southeast Asia, is traditionally valued for its medicinal and nutritional properties, particularly in promoting brain health. However, its neuroprotective potential against Alzheimer's disease (AD) remains underexplored. In this study, we investigated the therapeutic effects and safety of SBH in a rat model of AD. A total of sixty-three adult male Sprague-Dawley rats (180-200 g) were used: Fifteen were assigned to three toxicity groups (500, 750, 1000 mg/kg; <i>n</i> = 5) and forty-eight to six therapeutic groups (<i>n</i> = 8): Normal control, AD (AlCl₃ + D-gal), AD + Donepezil (1.5 mg/kg), and three SBH-treated groups (500, 750, 1000 mg/kg). Alzheimer-like pathology was induced by aluminium chloride (150 mg/kg) and D-galactose (300 mg/kg), followed by 14 days of treatment. Toxicity was evaluated through liver and kidney histopathology, while behavioural performance was assessed using the Open Field Test and Morris Water Maze. Serum dopamine, serotonin, corticosterone, and acetylcholinesterase activity were quantified via ELISA, and hippocampal morphology was examined histologically. SBH administration produced no signs of systemic toxicity and significantly improved exploratory activity and spatial learning, with the most pronounced effects at 750 mg/kg. Biochemical assays showed reduced acetylcholinesterase and corticosterone levels alongside increased dopamine and serotonin concentrations. Histological analysis confirmed neuronal preservation and reduced hippocampal damage. Inclusion of Donepezil as a positive control enabled comparison with a standard pharmacological treatment. These findings demonstrated that SBH is a safe and promising natural therapeutic capable of alleviating cognitive deficits associated with AD.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"13 1","pages":"1-28"},"PeriodicalIF":4.3,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric symptoms in mild cognitive impairment and early Alzheimer's disease: Clinical pattern and diagnostic implications.","authors":"Donna de Levante Raphael","doi":"10.3934/Neuroscience.2025032","DOIUrl":"10.3934/Neuroscience.2025032","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) and mild cognitive impairment (MCI) are widely recognized for their hallmark cognitive deficits, typically characterized by progressive cognitive deterioration. However, neuropsychiatric symptoms (NPS), including depression, apathy, anxiety, irritability, and sleep disturbances, are increasingly prevalent in the early stages of these conditions and significantly influence the disease trajectory and patient outcomes. Importantly, neuropsychiatric symptoms often precede overt memory loss by several years, with subtle mood and behavioral disturbances serving as early pre-diagnostic markers of an underlying Alzheimer's pathology. Their presence complicates the diagnosis, accelerates the disease progression, and intensifies the caregiver burden. However, distinguishing NPS arising from neurodegeneration and primary psychiatric disorders remains a profound diagnostic challenge, thus delaying timely intervention and obscuring early disease recognition.</p><p><strong>Objective: </strong>This structured narrative review examines the diagnostic complexities, clinical impact, and current management of NPS in early-stage Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI), alongside the biological underpinnings, clinical relevance, diagnostic challenges, and treatment perspectives. We argue that understanding and managing NPS is essential to improve the clinical outcomes, reduce the caregiver burden, and guide therapeutic innovation.</p><p><strong>Methods: </strong>A structured narrative review of peer-reviewed studies published between 2012 and 2025 was conducted using PubMed, MEDLINE, Scopus, PsycINFO, Google Scholar, and CINAHL. The included studies investigated NPS prevalence, neurobiological correlations, and management strategies in individuals with AD or MCI.</p><p><strong>Findings: </strong>NPS affects up to 80% of individuals with early AD or MCI, often preceding cognitive decline. The current management strategies heavily rely on non-pharmacological interventions such as caregiver support, behavioral activation, and structured routines, while pharmacological options remain limited by modest efficacy and safety concerns.</p><p><strong>Discussion: </strong>Advancing knowledge of NPS and their association with cognitive decline is critical to establish more precise diagnostic criteria and to inform personalized therapeutic approaches. Future research should emphasize biomarker-driven diagnostics and the development of novel, targeted interventions that simultaneously address cognitive and neuropsychiatric domains to optimize outcomes for patients and caregivers. This study contributes to the field by reframing NPS as potential early biomarkers in the trajectory of MCI and dementia progression.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"676-705"},"PeriodicalIF":2.7,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Excitatory/Inhibitory balance in autism spectrum disorders: Integrating genetic, neurotransmitter and computational perspectives.","authors":"Dilip Madia, Mujibullah Sheikh, Anil Pethe, Darshan Telange, Surendra Agrawal","doi":"10.3934/Neuroscience.2025031","DOIUrl":"10.3934/Neuroscience.2025031","url":null,"abstract":"<p><p>Computational modeling of excitatory/inhibitory (E/I) balance offers transformative insights into the neurobiological underpinnings of autism spectrum disorder (ASD). In this review, we examined the integration of neurotransmitter dynamics and genetic factors into multiscale computational frameworks to elucidate the mechanisms driving E/I dysregulation in ASD. We explored the pivotal roles of glutamate and GABA, the primary excitatory and inhibitory neurotransmitters, and the modulatory impact of serotonin and dopamine (DA), in shaping neural circuit stability, behavioral outcomes, and ASD core symptoms. Genetic mutations affecting synaptic proteins such as SHANK3, GRIN2A, and GABRB3 were highlighted for their capacity to disturb synaptic scaffolding and glutamatergic and GABAergic signaling, thereby shifting the E/I ratio. Computational approaches, ranging from detailed neuronal simulations to neural mass and spiking network models, captured the heterogeneous manifestations of E/I imbalance and aligned with molecular, neuroimaging, and electrophysiological findings in ASD. We discussed how these models informed individualized diagnostic strategies, enabled prediction of treatment responses, and offered targets for precision medicine. Major challenges included methodological inconsistencies, neurochemical measurement discrepancies, polygenic interactions, and the translation of model predictions into clinical practice. We concluded that the integration of neurotransmitter and genetic data within advanced computational models represents a significant advance toward unraveling ASD pathophysiology, with the promise of developing dynamic, personalized interventions. Ongoing efforts should emphasize longitudinal data, multiomic integration, sex-specific trajectories, and cross-disciplinary collaboration to further the clinical applicability and translational potential of computational E/I balance modeling in autism research.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"635-675"},"PeriodicalIF":2.7,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal and structural transformations in the caregiver's brain: Examining themes in parental neurobiology.","authors":"Elaine K Feller, Erin N McGinity, Patrick William Cafferty","doi":"10.3934/Neuroscience.2025030","DOIUrl":"10.3934/Neuroscience.2025030","url":null,"abstract":"<p><p>When becoming a parent, caregivers undergo complex, and sometimes permanent, neurobiological alterations, and this area of neurobiology has been extensively studied for decades. Due to ethical concerns and experimental limitations, the first parental neurobiology experiments were exclusively performed using rodent animal model systems, such as mice, rats, and voles. More recent technological advancements, such as the functional MRI (fMRI) scan, have become widely adopted and led to great insight into the impact of parenting on human neurobiology. In this thematic literature review, we present key studies that provide insight into the relationship of pregnancy and parturition on maternal caregiving behavior and the relationship of postpartum on all parents. First, we examine the relationship of endocrine hormones such as estrogen, progesterone, oxytocin, and testosterone with the neurobiological development of a parent. Next, we describe the significant transformation of subcortical maternal circuit components that occur during pregnancy, and the changes in the volume of grey and white matter generated during the postpartum. These brain structure alterations contribute to the development of parental nurturing behaviors.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"614-634"},"PeriodicalIF":2.7,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Personalized neural responses to self and filial reward: Functional and structural responses to motivational cues.","authors":"Siti Mariam Roslan, Siti Hajar Zabri, Nur Ayunie Ayob, Aini Ismafairus Abd Hamid, Nur Hartini Mohd Taib, Rahimah Zakaria, Sofina Tamam, Hazim Omar, Alwani Liyana Ahmad, Wan Mohd Zahiruddin Wan Mohammad, Aleya Aziz Marzuki, Asma Hayati Ahmad","doi":"10.3934/Neuroscience.2025029","DOIUrl":"10.3934/Neuroscience.2025029","url":null,"abstract":"<p><p>Understanding how individuals interact with reward-related cues in their environment provides insight into the neural mechanisms underlying motivation and personalized behavior. While monetary rewards for self are well studied, the neural basis of socially relevant rewards-such as filial reward-remains less understood. This study investigated functional and structural brain responses to reward gained from a cognitive task performance for self or for parents (filial) using functional MRI (fMRI) and diffusion MRI (dMRI) in young adults, reflecting personalized interaction with environmental cues. Thirty-two healthy young adults (17 males, mean age = 23 ± 1 years) performed a 2-back working memory task cued for reward conditions for self and for parents during fMRI scanning, followed by dMRI acquisition. Participants were categorized based on the reward condition in which they showed the highest score in task performance. Self-reported reward responsiveness scores were also collected. Random-effects fMRI analysis revealed activation of the putamen in the self-reward condition, more than in the filial reward condition. Using this region as a seed, probabilistic tractography was conducted to compute connection probability indices (CPI) to key target areas: anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), dorsolateral and ventrolateral prefrontal cortices, anterior/posterior insula, and amygdala. The nucleus accumbens (NAcc) was included as a comparative seed. While the cue for self-reward elicited activation in the reward area putamen, with higher white matter connectivity from the right putamen to the ACC, a cue for filial reward significantly activated the right insula. Lateralization to the right insula was also seen in the structural connectivity to NAcc in the filial group. Filial reward also displayed a positive relationship between white matter connectivity of left NAcc to PCC with reward responsiveness. These results demonstrate individualized neural responses shaped by the self and social relevance of the reward.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"593-614"},"PeriodicalIF":2.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute whole-body vibration therapy enhances cognitive speed without altering heart rate variability in healthy young adults.","authors":"Zaw Myo Hein, Nisha Shantakumari, Yazan Ayman Khaoli, Che Mohd Nasril Che Mohd Nassir","doi":"10.3934/Neuroscience.2025028","DOIUrl":"10.3934/Neuroscience.2025028","url":null,"abstract":"<p><p>Whole-body vibration therapy (WBVT) is increasingly recognized as an alternative exercise modality with established benefits for musculoskeletal and cardiovascular health. Its effects on cognitive performance and autonomic regulation in healthy young adults, however, remain unclear. This within-subject study investigated whether acute WBVT influences executive function and heart rate variability (HRV). Thirty-six healthy volunteers (aged 18-25 years) completed two testing sessions separated by 7 days: a baseline (no vibration) session and a single 10-min WBVT session performed in a standing posture. Cognitive performance was assessed immediately after each session using a modified Stroop test, and electrocardiographic recordings were analyzed for HRV indices, including stress index, low-frequency (LF) and high-frequency (HF) power, LF/HF ratio, and mean heart rate. Compared with baseline, WBVT was associated with faster mean reaction times for congruent and incongruent Stroop stimuli (all p < 0.001) without changes in response accuracy. The stress index increased during the Stroop task relative to baseline (p = 0.052) and returned toward baseline following WBVT, whereas LF, HF, the LF/HF ratio, and total power showed no statistically significant changes. In this cohort, acute WBVT was associated with improved processing speed without measurable alterations in standard HRV metrics. These preliminary findings suggest that WBVT may transiently facilitate attentional processing in healthy young adults, but controlled trials with sham conditions and mechanistic measures are needed to confirm and contextualize these effects.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"570-591"},"PeriodicalIF":2.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Remyelination as a therapeutic target in the treatment of multiple sclerosis.","authors":"Gurprit Kaur Garcha, Mohamed Ahmed","doi":"10.3934/Neuroscience.2025027","DOIUrl":"10.3934/Neuroscience.2025027","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) affecting young adults, particularly in North America and Europe, with nearly 2.5 million individuals impacted globally. Characterized by demyelination and neuronal damage, MS involves complex immune-mediated mechanisms. In this review, we focused on the pathophysiological processes of MS, highlighting the roles of T cells, B cells, and proinflammatory cytokines in driving demyelination, which are often the main focus of treatments in the form of immunotherapy. We emphasized remyelination as a key therapeutic target that is necessary for protecting axons and restoring neural function to solve the root problem. Emerging therapies, such as high-dose supplementation with vitamin D and glutathione, appear effective in regulating immune activity and lowering oxidative burden, thus supporting remyelination and neuroprotection. Preclinical models using toxin-induced demyelination have provided valuable insights into the mechanisms of remyelination and identified potential therapeutic targets like LINGO-1 antagonists. Clinical trials, particularly those involving the anti-LINGO-1 monoclonal antibody BIIB033, have demonstrated encouraging results in enhancing remyelination and improving clinical outcomes. LINGO-1 is an inhibitory protein that impairs OPC differentiation. Integrating these innovative approaches into clinical practice could revolutionize MS management by shifting the focus from managing symptoms to promoting CNS repair and long-term recovery. Continued research into the molecular mechanisms of remyelination and the development of targeted therapies is essential for advancing MS treatment and improving the quality of life for patients.</p>","PeriodicalId":7732,"journal":{"name":"AIMS Neuroscience","volume":"12 4","pages":"539-569"},"PeriodicalIF":2.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12782952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145950980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}