CNS & neurological disorders drug targets最新文献

{"title":"Trends and Advancements in Smart Electrospun Food Fibers for the Management of Neurological Disorders.","authors":"Sejal Porwal, Rishabha Malviya, Sathvik Belagodu Sridhar, Tarun Wadhwa, Javedh Shareef, Dhanalekshmi Unnikrishnan Meenakshi","doi":"10.2174/0118715273375873250829060106","DOIUrl":"https://doi.org/10.2174/0118715273375873250829060106","url":null,"abstract":"<p><p>Neurological disorders are complex conditions characterized by impairment of the nervous system, affecting motor, cognitive, and sensory functions. Current treatments meet substantial obstacles, primarily due to the difficulty of transporting drugs across the blood-brain barrier and ineffective therapy for nerve regeneration. Emerging technologies, such as electrospinning, offer innovative solutions to overcome these challenges. The study explores the potential of electrospun food fibers in managing and treating neurological disorders, concentrating on their role in drug delivery and nerve tissue regeneration. Electrospinning allows for the generation of nanofibers from diverse natural and synthetic polymers that imitate the extracellular matrix and stimulate brain healing. These fibers may be loaded with therapeutic drugs, permitting controlled, localized drug release while limiting systemic toxicity. For instance, electrospun fibers loaded with neuroprotective drugs, such as donepezil and levodopa, have exhibited better drug stability, enhanced bioavailability, and prolonged therapeutic efficacy in treating syndromes such as Alzheimer's and Parkinson's diseases. Furthermore, the biodegradable and biocompatible nature of food-based polymers like chitosan, cellulose, and zein makes them great candidates for medicinal applications, minimizing the risk of inflammation and unfavorable immunological reactions. In conclusion, electrospun food fibers show tremendous promise in resolving the issues of drug delivery and nerve regeneration in neurological illnesses. Their capacity to boost therapeutic results via targeted and regulated drug release makes them a possible alternative to established treatment procedures, bringing renewed hope to patients suffering from neurodegenerative disorders.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145031340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Anesthetic to Neuroprotector: Multi-Omics Reveals Ketamine's Previously Unexplored Neuroprotective Role in Alzheimer's Disease.","authors":"Yue Gong, Tian Yu, Yan Zhou, Yilin Zhu, Wenlong Du, Xiaodong Xu","doi":"10.2174/0118715273396403250825131703","DOIUrl":"10.2174/0118715273396403250825131703","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) lacks effective biomarkers and diseasemodifying therapies. This study explored transcriptomic dysregulation, immune-metabolic crosstalk, and drug repurposing opportunities in AD.</p><p><strong>Methods: </strong>Transcriptomic datasets (GSE109887, GSE5281) were harmonized using batch correction. Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-Expression Network Analysis (WGCNA) prioritized AD-associated modules. Machine learning (RF+LDA) validated diagnostic genes across external cohorts (GSE29378, GSE122063). Functional enrichment, immune infiltration (CIBERSORT), single-cell analysis (AlzData), Mendelian randomization (MR), and drug repurposing (DSigDB/CB-Dock2) were employed.</p><p><strong>Results: </strong>WGCNA identified the yellow module as most AD-relevant. Machine learning prioritized 15 diagnostic genes (e.g., CASP6, LDHA, CHRM1), achieving AUCs of 0.941 (training) and 0.715- 0.910 (validation). Single-cell analysis confirmed their dysregulation in AD brains. MR revealed FIBP as a protective factor, inversely linked to AD risk. Immune profiling showed increased naive B cells and M1 macrophages in AD. Ketamine exhibited the highest drug enrichment (fold enrichment = 49.12), with strong binding to CASP6 (-5.3 kcal/mol), CHRM1 (-7.8 kcal/mol), and LDHA (-6.7 kcal/mol).</p><p><strong>Discussion: </strong>CASP6, LDHA, and CHRM1 underpin immune-metabolic dysregulation in AD. Ketamine targets these genes, suggesting therapeutic potential. FIBP's protective role and naive B-cell shifts offer novel mechanistic insights.</p><p><strong>Conclusion: </strong>This integrative study identifies robust diagnostic biomarkers and nominates ketamine for repurposing in AD. Experimental validation of ketamine's neuroprotective effects and FIBP's role is warranted.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence of the Efficacy of Acetylcholinesterase Inhibitors in In Vivo Studies: A Systematic Review.","authors":"Franciane N Souza, Everson S David, Henrique B Lima, Abraão G Silva, Raimundo Nonato P Souto, Lorane I S Hage-Melim","doi":"10.2174/0118715273388078250801044226","DOIUrl":"https://doi.org/10.2174/0118715273388078250801044226","url":null,"abstract":"<p><strong>Introduction: </strong>This systematic review aimed to provide an updated overview of studies using anticholinesterases with in vivo activity for the treatment of Alzheimer's disease.</p><p><strong>Methods: </strong>A systematic review was conducted using searches in the following databases: PubMed, SciELO (Scientific Electronic Library Online), Web of Science, LILACS (Latin American and Caribbean Literature in Health Sciences), as well as gray literature, through the CAPES and Google Scholar databases of national and international journals. The research was registered on the International Prospective Register of Systematic Reviews (PROSPERO) platform under registration number: CRD42024482117 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol.</p><p><strong>Results: </strong>A total of 1,191 articles were identified in the databases, of which 11 were selected to compose this systematic review, as they met the previously pre-defined selection criteria. The selected articles were published between 2019 and 2023. The substance most commonly used to induce Alzheimer's was scopolamine. As for administration routes, the most used was intraperitoneal. Some of the methods used to evaluate cognitive processes in rats and mice were- Elevated Plus Maze (EPM), Morris water maze (MWZ), Y maze, and passive avoidance tests.</p><p><strong>Discussion: </strong>The reviewed studies demonstrated that the evaluated anticholinesterase agents exhibited anti-Alzheimer activity in animal models, with notable cognitive effects observed in behavioral tests.</p><p><strong>Conclusion: </strong>The data indicated that the analyzed anticholinesterase agents have therapeutic potential for Alzheimer's disease, justifying the continuation of preclinical research and future clinical investigations.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144982633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organosulfur Compounds: Potential Therapeutics for Parkinson's Disease.","authors":"Melford Chuka Egbujor","doi":"10.2174/0118715273386239250706125440","DOIUrl":"https://doi.org/10.2174/0118715273386239250706125440","url":null,"abstract":"<p><p>Several organosulfur compounds exhibit anti-Parkinson's disease (PD) activities. PD is a progressive and chronic neurodegenerative condition that causes motor and non-motor symptoms that severely reduce quality of life. A selective loss of dopaminergic neurons in the substantia nigra, in addition to several neuropathological mechanisms, has been implicated in PD. The present therapeutic techniques are mostly focused on providing symptomatic relief and frequently have significant side effects, which underscores the pressing need for innovative medicines that address the underlying causes of disease. Several organosulfur compounds, both synthesized and naturally occurring analogues, have gained attention as potential anti-PD molecules because of their wide range of biological activities, which include anti-inflammatory, neuroprotective, and antioxidant capabilities. Several organosulfur compounds have been shown to have potential neuroprotective benefits in preclinical research on PD. Their ability to attenuate neuroinflammation, oxidative stress, apoptosis, and mitochondrial dysfunction, which are central to PD pathogenesis via modulation of cellular pathways and endogenous antioxidant defenses, provides multifaceted approaches to neuroprotection in PD. Thus, the current review provides the state of the art on the potential therapeutic effects of organosulfur compounds in PD. The natural and synthetic sources of anti-PD organosulfur compounds, including their physical properties, chemical properties, structure-activity relationship (SAR), and therapeutic effects in PD, were discussed. The challenges and future directions of organosulfur compounds as potential anti-PD drugs and their clinical trial prospects were also highlighted. This is aimed at paving the way for the development of more effective and sustainable treatment strategies for PD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurosarcoidosis - Epidemiological, Clinical, Diagnostic, and Therapeutic Aspects: A Systematic Review.","authors":"Jamily Izabel Alves Dos Santos, Valéria Dos Santos Turbano, Ana Tercia Mendes Carneiro, Bruno Farias Oliveira, Lucas Gregório Batista, Argemiro Érick Landim Grangeiro, Pedro Joabe de Assis Silva, Alyne Layane Pereira Lemos, Gislene Farias de Oliveira, Hermes Melo Teixeira Batista, Marco Felipe Macêdo Alves, Jucier Gonçalves Junior","doi":"10.2174/0118715273381216250706103418","DOIUrl":"https://doi.org/10.2174/0118715273381216250706103418","url":null,"abstract":"<p><strong>Introduction: </strong>Neurosarcoidosis is a rare and severe manifestation of sarcoidosis, whose natural history still lacks a comprehensive and theoretical understanding. Therefore, we aimed to conduct a qualitative systematic review of the literature on the clinical-epidemiologic, diagnostic, and therapeutic assessment of patients with neurosarcoidosis.</p><p><strong>Methods: </strong>A qualitative systematic literature review was conducted in accordance with the PRISMA protocol. The search was conducted between January 1954 and December 2024 in the following databases: PubMed, Scopus, Web of Science, CAPES Journal Portal, and the Virtual Health Library (VHL). Articles were selected if they had at least one of the selected descriptors in the title or abstract, were written in English, Portuguese, or Spanish, and dealt with the clinical-epidemiologic, diagnostic, and therapeutic aspects of neurosarcoidosis. Review articles, experimental studies, and short communications were excluded from the analysis.</p><p><strong>Results: </strong>Seventy-four articles with 551 cases of neurosarcoidosis were included. The majority of studies were case reports, followed by cohort studies conducted in European countries. The methodological quality of most studies was \"good\".</p><p><strong>Discussion: </strong>Patients with neurosarcoidosis are primarily women Caucasian ethnicity with a mean age of 43.5 years. The disease most commonly involves the cranial nerves (especially cranial nerve II), followed by aseptic meningitis, panhypopituitarism, ocular changes, and diabetes insipidus. The most common laboratory findings were cerebrospinal fluid abnormalities, hypogonadotropic hypogonadism, hyperprolactinemia, and hypothyroidism. The most common neuroimaging changes were meningeal enhancement and pituitary destruction. The treatment of choice was glucocorticoids in conjunction with or without immunosuppressants, with methotrexate and azathioprine being the most commonly used.</p><p><strong>Conclusion: </strong>This review identified that manifestations such as cranial nerve alterations, aseptic meningitis, and pituitary infiltrations are frequent patterns in neurosarcoidosis, generally associated with laboratory and imaging findings that aid in the diagnosis. Systematizing these data provides a broad view of the disease and may contribute to early diagnosis and effective therapy. Nevertheless, longitudinal studies with larger samples are needed to better understand its natural history and clinical outcomes in the medium and long term.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Polymorphic Form of Sodium Benzoate (Ω-NaBen): Improved Solubility, Stability, Central Nervous System Effects, and Antipsychotic Activities via D-Amino Acid Regulation.","authors":"Wei-Hua Chang, Yi-An Lai, Hsing-Chun Tsai, Yi-Wen Mao, Madelynne Tsai, Chi-Sheng Kuo, Yi-Ying Shih, Lu-Ping Lu, Peng Tan, Guochuan Emil Tsai","doi":"10.2174/0118715273359634250626102333","DOIUrl":"https://doi.org/10.2174/0118715273359634250626102333","url":null,"abstract":"<p><strong>Introduction: </strong>Sodium benzoate (NaBen), a D-amino acid oxidase inhibitor, has been demonstrated to possess antipsychotic and cognition-enhancing effects in animal models. However, the clinical findings in patients with schizophrenia and dementia are mixed and inconclusive.</p><p><strong>Objectives: </strong>To further improve its therapeutic potential, a novel crystalline polymorph of NaBen (abbreviated as Ω-NaBen) was developed. This study evaluated the physicochemical properties and central nervous system (CNS) effects of Ω-NaBen and investigated its therapeutic potential.</p><p><strong>Methods: </strong>The novel crystalline structure of Ω-NaBen was confirmed by thermogravimetric analysis, differential scanning calorimetry, and X-ray powder diffractometry. Water solubility test and stability test were performed to compare its physicochemical properties. The CNS exposure and Damino acids levels in brain subregions of Ω-NaBen- and non-Ω-NaBen-treated male mice were determined with LC-MS/MS. Therapeutic effects of Ω-NaBen in the MK-801-induced mouse model were assessed by the open field test, novel object recognition test, and three-chamber social test.</p><p><strong>Results: </strong>Our findings indicated that Ω-NaBen had a unique crystalline structure and showed better aqueous solubility and crystal stability, either with or without clozapine, compared with amorphous NaBen. Ω-NaBen also showed improved CNS exposure and induced higher levels of D-serine or/and D-alanine in the brain. In MK-801-treated mice, Ω-NaBen displayed enhanced effects in alleviating hyperactivity and stronger potency in relieving cognitive impairment. It also improved efficacy in relieving social deficit, a negative symptom model of schizophrenia.</p><p><strong>Conclusion: </strong>Our study demonstrated Ω-NaBen's promising potential as a novel CNS therapeutic due to its favorable physicochemical properties, CNS exposure, and neurochemical and behavioral effects.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144651529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tau Pathology in Alzheimer's Disease: Bridging Molecular Mechanisms and Targeted Therapies.","authors":"Mini Dahiya, Monu Yadav, Anil Kumar, Chetan Goyal","doi":"10.2174/0118715273376581250626003322","DOIUrl":"https://doi.org/10.2174/0118715273376581250626003322","url":null,"abstract":"<p><p>Alzheimer's disease (AD), the leading cause of dementia, is characterized by β-amyloid (Aβ) plaques and neurofibrillary tangles of hyperphosphorylated tau. While Aβ-targeting therapies have been a primary focus of drug development, their long-term efficacy remains uncertain. Emerging evidence suggests that tauopathy is more closely linked to cognitive decline, positioning tau as a promising therapeutic target. Tauopathies, a group of neurodegenerative disorders marked by tau dysfunction and aggregation, were historically attributed to a toxic gain-of-function. However, clinical trials targeting tau have yielded limited success, likely due to the heterogeneity of tau pathology, variable patient responses, and suboptimal therapeutic strategies. Here, we underline the need for a refined understanding of tau biology to develop effective interventions. Advancing precision medicine approaches and identifying optimal tau species for therapeutic intervention could transform tau-targeting therapies into a cornerstone in managing tauopathies. By integrating insights from genetics, pathology, and translational research, future efforts may overcome current challenges and unlock novel treatment avenues, ultimately improving patient outcomes.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxicity of Endogenous Neurotoxin Salsolinol in Parkinson's Disease.","authors":"Shuang Wu, Yu'an Zhou, Qiang Li, Huiyan Sun, Lida Du, Hongquan Wang","doi":"10.2174/0118715273379940250704062355","DOIUrl":"https://doi.org/10.2174/0118715273379940250704062355","url":null,"abstract":"<p><p>Salsolinol (SAL), an endogenous neurotoxin 1-methyl-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline, is a dopamine metabolite that has been implicated in the pathogenesis of Parkinson's disease (PD) due to its selective toxicity toward dopaminergic (DA) neurons. Experimental studies have demonstrated that SAL induces DA neuronal injury both in vitro and in vivo, thereby contributing to the PD pathogenesis. Given its specificity for nigral DA neurons, SAL serves as a more relevant model for studying PD-associated brain waste clearance and neurotoxicity, as it recapitulates the progressive nature of the disease. Emerging evidence indicates that SAL exerts its neurotoxic effects primarily through the induction of oxidative stress and regulated cell death in DA neurons. With the escalating global burden of PD and unmet need for therapies targeting multifactorial mechanisms, the dual role of SAL as both a dopamine derivative and mediator of protein aggregation links metabolic dysfunction to neurodegeneration, positioning it as a pivotal target for understanding sporadic PD and therapeutic development. In this review, we summarize current knowledge on the molecular mechanisms underlying SAL-induced neurotoxicity and its pathophysiological role in PD. By elucidating these mechanisms, this review provides valuable insights for future research in uncovering underestimated molecular targets for therapeutic intervention in PD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDP-43 Proteinopathies in ALS and FTLD: Mechanistic Insights and Therapeutic Approaches.","authors":"Shilpi Chauhan, Preeti Maan, Archna Panghal","doi":"10.2174/0118715273374466250617085832","DOIUrl":"https://doi.org/10.2174/0118715273374466250617085832","url":null,"abstract":"<p><p>TAR DNA-binding protein 43 (TDP-43) is a vital RNA/DNA-binding protein involved in RNA metabolism, playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Approximately 97% of sporadic ALS (sALS), familial ALS (fALS) and FTLD cases are associated with pathological inclusions of hyperphosphorylated and ubiquitinated TDP-43 and genetic mutations in TAR DNA binding protein (TARDBP). Besides TARDBP, mutations in other genes such as C9ORF72, SOD1, FUS, and NEK1 are also linked to other fALS cases. Cytoplasmic mislocalization, aberrant post-translational modifications, and amyloid- like aggregation characterize TDP-43 pathology. These pathological changes impair essential cellular processes, including gene expression, mRNA stability, and RNA metabolism. Mechanisms of TDP-43-induced toxicity include disruption of endocytosis, mitochondrial dysfunction, and progressive cellular damage. Additionally, liquid-liquid phase separation (LLPS) and prion-like propagation are emerging as central features of its pathological spread. This review summarizes advances in understanding TDP-43's physiological functions and pathological mechanisms in ALS and FTLD. It highlights key processes underlying TDP-43 toxicity, such as aggregation, selective neuronal vulnerability, and regional susceptibility. Finally, this review summarizes evolving therapeutic strategies aimed at mitigating TDP-43-related toxicity through disaggregation, targeting mislocalization, and addressing upstream dysfunctions and challenges faced in the development of effective therapies for ALS and FTLD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144577249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Amyloid Pathways in Alzheimer's Disease: Mechanisms and Therapeutic Targets.","authors":"Sudha Bansal, Monu Yadav, Priyanka Bisht, Divyanshi Bansal, Shiva Tushir, Dev Rathore","doi":"10.2174/0118715273382447250526062100","DOIUrl":"https://doi.org/10.2174/0118715273382447250526062100","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a typical neurodegenerative illness, and it is a main cause of dementia, affecting millions of older populations throughout the world. Although the exact causes of AD are still not clear, the disorder is known to be considered by the accumulation of amyloid plaques and tau tangles in the neuronal cells. Currently, available drugs such as cholinesterase inhibitors and NMDA antagonists can help manage symptoms but don't address the underlying causes of the disease. New experimental treatments targeting amyloid and tau proteins show promise but are still in clinical trials. Recently, β-Amyloid has gained attention as an emerging target to develop new medications as it is strongly involved in the pathophysiology of AD. β-Amyloidpathies are directly or indirectly linked with multiple pathways, including GSK3β, insulin resistance, NMDA dysfunction, AMP-activated kinase, cholesterol mechanism, mitochondrial dysfunction, neuroinflammation, and SIRT1. However, several β-Amyloid targeting therapies employing various mechanisms have shown partial success in clinical trials, possibly due to a lack of understanding of the molecular link of this peptide with other pathways. Therefore, this paper has discussed the β- Amyloid molecular mechanisms involved in pathophysiological pathways to manage neuronal disorders and intracellular signal transduction effectively.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144531715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}