Rohinee Dodiya, Pratishtha Sharma, Dipa Israni, Mohammad Amjad Kamal, Nigel H Greig
{"title":"Zebrafish-Based Parkinson's Disease Models: Unveiling Genetic Mechanisms and Therapeutic Pathways.","authors":"Rohinee Dodiya, Pratishtha Sharma, Dipa Israni, Mohammad Amjad Kamal, Nigel H Greig","doi":"10.2174/0118715273367688250528122144","DOIUrl":"https://doi.org/10.2174/0118715273367688250528122144","url":null,"abstract":"<p><p>The zebrafish (Danio rerio) is widely utilised as a live vertebrate model in research on neurological development and nervous system diseases. This species exhibits various distinctive attributes that render it well-suited for investigating neurological disorders such as Parkinson's disease (PD). Zebrafish and humans have a genetic similarity of around 70%, and approximately 84% of the genes associated with human diseases have zebrafish equivalents. The genetic similarities and presence of neurotransmitters like dopamine allow scientists to study PD genes and proteins. Zebrafish are often challenged with neurotoxins to induce Parkinsonian symptoms, allowing researchers to evaluate attendant biochemical pathways. Zebrafish can also repair damaged organs, increasing their potential value in PD research. Because of their regenerative capacity and genetic resemblance to humans, these species can be used to study dopamine neurodegeneration and prospective PD treatments. In addition to PD, zebrafish are helpful models for studying Huntington's disease, Alzheimer's disease, epilepsy, depression, schizophrenia, and anxiety disorders. This article emphasizes significant findings of relevance to PD using the zebrafish model, describing its challenges and benefits. The investigation of key genes, protein pathways, and neurotoxins provides the opportunity to facilitate understanding of the role of dopamine neurotransmitters in PD and expedite the development of potentially promising therapeutic strategies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287587","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":"Mechanisms and Mitochondria-targeted Therapies for Retinal Ganglion Cell Degeneration in Glaucoma.","authors":"Juanjuan Guan, Haibo Li, Kun Xiong","doi":"10.2174/0118715273397014250604050651","DOIUrl":"https://doi.org/10.2174/0118715273397014250604050651","url":null,"abstract":"","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287586","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}
Muhammad Asif, Hamid Ullah, Nelofer Jamil, Musarat Riaz, Maryam Zain, Peter Natesan Pushparaj, Mahmood Rasool
{"title":"Advances in Diagnostic Approaches for Alzheimer's Disease: From Biomarkers to Deep Learning Technology.","authors":"Muhammad Asif, Hamid Ullah, Nelofer Jamil, Musarat Riaz, Maryam Zain, Peter Natesan Pushparaj, Mahmood Rasool","doi":"10.2174/0118715273374284250519053646","DOIUrl":"https://doi.org/10.2174/0118715273374284250519053646","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a devastating neurological disorder that affects humans and is a major contributor to dementia. It is characterized by cognitive dysfunction, impairing an individual's ability to perform daily tasks. In AD, nerve cells in areas of the brain related to cognitive function are damaged. Despite extensive research, there is currently no specific therapeutic or diagnostic approach for this fatal disease. However, scientists worldwide have developed effective techniques for diagnosing and managing this challenging disorder. Among the various methods used to diagnose AD are feedback from blood relatives and observations of changes in an individual's behavioral and cognitive abilities. Biomarkers, such as amyloid beta and measures of neurodegeneration, aid in the early detection of Alzheimer's disease (AD) through cerebrospinal fluid (CSF) samples and brain imaging techniques like Magnetic Resonance Imaging (MRI). Advanced medical imaging technologies, including X-ray, CT, MRI, ultrasound, mammography, and PET, provide valuable insights into human anatomy and function. MRI, in particular, is non-invasive and useful for scanning both the structural and functional aspects of the brain. Additionally, Machine Learning (ML) and deep learning (DL) technologies, especially Convolutional Neural Networks (CNNs), have demonstrated high accuracy in diagnosing AD by detecting brain changes. However, these technologies are intended to support, rather than replace, clinical assessments by medical professionals.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188657","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":"The NLRP3-P2X7 Axis and Cytokine Crosstalk in Alzheimer's Disease: Mechanisms, Implications, and Therapeutic Opportunities.","authors":"Shubham Kurmi, Gaurav Doshi, Siddhi Bagwe Parab","doi":"10.2174/0118715273377780250505115039","DOIUrl":"https://doi.org/10.2174/0118715273377780250505115039","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the primary cause of dementia in elderly individuals, characterized by progressive memory loss, cognitive decline, and impaired daily functioning. Pathologically, AD is associated with the accumulation of amyloid-β (Aβ) plaques, tau tangles, mitochondrial dysfunction, and chronic neuroinflammation. The activation of the NOD-like receptor pyrin domain- containing 3 (NLRP3) inflammasome by Aβ clusters triggers microglial activation, leading to a cascade of inflammatory responses. Similarly, tau tangles stimulate neuronal and glial cells, further amplifying NLRP3 activation and perpetuating a cycle of chronic inflammation. Mitochondrial dysfunction exacerbates this process by increasing oxidative stress and inflammasome activation. Additionally, purinergic receptor P2X7 (P2X7R) activation in microglia plays a crucial role in initiating neuroinflammation, making it a potential therapeutic target. Despite extensive research, current AD therapies remain symptomatic rather than disease-modifying. Targeting the NLRP3 inflammasome offers a promising strategy for mitigating AD progression. Various small-molecule inhibitors, monoclonal antibodies, and repurposed drugs have been explored to inhibit NLRP3 activation and its downstream signaling pathways. Preclinical studies suggest that NLRP3 inhibitors effectively reduce Aβ- and tau-induced neuroinflammation while improving mitochondrial function and overall neuronal survival. This review summarizes NLRP3 inflammasome priming, activation, and the therapeutic potential of its inhibitors in AD, highlighting challenges such as tau pathology, biomarker limitations, and treatment optimization. While NLRP3 remains a promising target, most inhibitors are in the early stages with uncertain long-term efficacy and BBB penetration. Future research should explore genetic variability, sex differences, and alternative approaches to enhance neuroprotective strategies.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144961","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}
Siddig Ibrahim Abdelwahab, Manal Mohamed Elhassan Taha, Hassan Ahmad Ahmad Alfaifi, Amal Hamdan Alzahrani, Ieman A Aljahdali, Omar Oraibi, Sohaila Ali, Bassem Oraibi, Abdullah Farasani, Ahmed Ali Jerah, Yasir Osman Hassan Babiker, Anas A Ahmed, Gassem Gohal, Osama Albasheer
{"title":"Trends in Research on Gantenerumab for Alzheimer's Disease: A Bibliometric and Thematic Analysis.","authors":"Siddig Ibrahim Abdelwahab, Manal Mohamed Elhassan Taha, Hassan Ahmad Ahmad Alfaifi, Amal Hamdan Alzahrani, Ieman A Aljahdali, Omar Oraibi, Sohaila Ali, Bassem Oraibi, Abdullah Farasani, Ahmed Ali Jerah, Yasir Osman Hassan Babiker, Anas A Ahmed, Gassem Gohal, Osama Albasheer","doi":"10.2174/0118715273349645250324040257","DOIUrl":"https://doi.org/10.2174/0118715273349645250324040257","url":null,"abstract":"<p><strong>Background: </strong>Gantenerumab (GR), a promising therapeutic agent for Alzheimer's disease (AD), has been the subject of extensive research. In this study, we aimed to provide a comprehensive analysis of the literature on GR.</p><p><strong>Methods: </strong>A systematic search was conducted using the PubMed, Scopus, and Web of Science databases. VOSviewer and Bibliometrix were utilized to analyze bibliographic data.</p><p><strong>Results: </strong>The analysis of the literature on GR revealed distinct publication trends. Reviews accounted for 52% of the records, followed by research articles (31%). The United States contributed the highest proportion of publications (26%). The Journal of Prevention of Alzheimer's Disease was the most prolific source (21 articles). The annual number of publications increased steadily from 2009 to 2024. Major international collaborations were observed among the United States, the United Kingdom, Switzerland, France, and Sweden. Research activity consistently centered on key themes, such as amyloid imaging, biomarkers, clinical trials, and β-amyloid. Thematic mapping identified specialized subfields, core research areas, and dynamic shifts in topics, offering a comprehensive overview of the GR research landscape.</p><p><strong>Conclusion: </strong>GR-related literature showed sustained thematic focus, growing international collaboration, and a steady rise in publication volume within the field of AD. These findings highlight the continued need for clinical and biomarker-focused investigations to advance therapeutic development in AD.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103320","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}
May Majed Alqurashi, Ayman Mohammed Al-Sulami, Mohammed Bayamin, Faris Abdullaha Al Toub, Mustafa Zeyadi, Salma Naqvi, Mirza Rafi Baig, Fahad A Al-Abbasi, Shaikh Gazi, Omar A Al-Bar, Vikas Kumar, Firoz Anwar
{"title":"Early Detection of Glioma: Investigating Inflammatory Markers (CRP), Kidney, and Liver Function.","authors":"May Majed Alqurashi, Ayman Mohammed Al-Sulami, Mohammed Bayamin, Faris Abdullaha Al Toub, Mustafa Zeyadi, Salma Naqvi, Mirza Rafi Baig, Fahad A Al-Abbasi, Shaikh Gazi, Omar A Al-Bar, Vikas Kumar, Firoz Anwar","doi":"10.2174/0118715273360604250420020956","DOIUrl":"https://doi.org/10.2174/0118715273360604250420020956","url":null,"abstract":"<p><strong>Background: </strong>Glioma, a global concern, a rare but aggressive brain cancer, poses a unique challenge for health scientists. The diagnosis solely depends on Magnetic resonance imaging (MRI) and computed tomography (CT) scans, which are effective but may lead to misinterpretation.</p><p><strong>Objective: </strong>The present study explores outcomes and develops effective strategies for early detection of glioma. The study also focuses on exploring a comprehensive panel of blood biochemical parameters in this challenging landscape.</p><p><strong>Methods: </strong>A retrospective study included all adults above 18 years (n=78) diagnosed with Glioma and admitted to King Abdullah Medical City, Mecca. Routine blood biochemistry of whole blood was performed, showing Glioma either IDH mutant or Wild type detected via standard protocol.</p><p><strong>Results: </strong>Demographic variations categorized by age, gender, nationality, Glioma types, and subtypes, revealing a predominant occurrence in the 51-60 age range. Among gliomas, 33.3% were IDH Mutant, while the remaining 66.7% were Wild type, with Glioblastoma (wild type) being the most prevalent at 64.1%. Creatinine levels (0.60 ± 0.17 mg/dL, p<0.2) and urea levels (4.14 ± 1.55 mg/dL, p<0.05) were lower in females, while alkaline phosphatase (74.90 ± 25.17 uL, p<0.3) and total bilirubin (0.38 ± 0.20 mg/dL, p<0.01) also showed significant differences. Neutrophils were significantly lower in females (4.51 ± 2.31 uL, p<0.01), with elevated lymphocytes (7.46 ± 3.14 uL) and CRP (4.65 ± 7.98 mg/dL, p<0.001). The mutant type had lower levels of ALP (78.46 ± 29.08 uL), AST (22.30 ± 11.06 uL), ALT (30.06 ± 19.22 uL), and GGT (66.15 ± 40.76 uL) compared to the wild type (ALP: 86.98 ± 30.33 uL, AST: 29.98 ± 15.10 uL, ALT: 36.32 ± 20.94 uL, GGT: 83.44 ± 45.91 uL). GGT showed significant variation (p<0.01), with higher neutrophil levels in the wild type (5.69 ± 4.12 uL) compared to the mutant (3.82 ± 2.28 uL). Lymphocytes (4.84 ± 22.94 uL) and CRP (4.29 ± 6.87 mg/dL) were significantly higher (p<0.001) in the wild type.</p><p><strong>Conclusion: </strong>Altered KFL and LFT in Mutant and wild-form Glioma depend upon the gender of patients. Combining these biochemical parameters with existing imaging modalities such as MRI and CT could potentiate the diagnostic accuracy of Glioma, offering a more comprehensive approach to patient care. While insightful, the findings do not replace the crucial role of imaging techniques but could complement them in a multi-model diagnostic approach.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031864","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":"Unraveling the Triad: A Bioinformatics Analysis of the Interplay between Prenatal Depression, Inflammation, and the Gut Microbiota.","authors":"Wafaa Taha, Oumaima Anachad, Houssam Assioui, Chaimaa Saadoune, Asmae Taheri, Mariame El Messal, Faiza Bennis, Fatima Chegdani","doi":"10.2174/0118715273371682250421053159","DOIUrl":"https://doi.org/10.2174/0118715273371682250421053159","url":null,"abstract":"<p><strong>Background: </strong>Prenatal depression is a prevalent mental disorder that affects women during pregnancy. Alterations in the maternal microbiota have been linked to changes in the composition of the intestinal microbiota of foetus, which can have long-term consequences for the child's health. The gut-brain axis, which involves bidirectional communication between the gut and the brain, is believed to play a role in the development of depression.</p><p><strong>Methods: </strong>This study aimed to gather evidence for both the influence of microbiota and immunity on depression during pregnancy, using integrated bioinformatics analysis. A set of 219 differentially expressed genes (DEGs) associated with prenatal depression was established to correlate with gut inflammation. DEG data were collected from different bibliographic sources with fold change >1 and adjusted p-value <0.05. Moreover, 205 DEGs were annotated using String software.</p><p><strong>Results: </strong>The protein-protein interaction networks of DEGs obtained were determined by 16 main genes: IL6, IFNG, IL1B, IL10, CD4, CXCL8, CCL2, IL2, CCL5, IL4, TGFB1, IL13, IL17A, TLR4, CRP, and BDNF. The enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was conducted using SRplot and clusterProfiler. They were significantly involved in prenatal depression and associated with inflammation and gut microbiota.</p><p><strong>Conclusion: </strong>This study identified core genes that contribute to the understanding of the molecular mechanisms involved in the development of prenatal depression, which may serve as targets for early diagnosis, prevention, and treatment.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002611","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":"Flavonoids in Brain Ischemia-Reperfusion and their Effect on Kinases as Signaling Pathway Activity.","authors":"Esra Gulsum Danis, Rasim Mogulkoc, Abdulkerim Kasim Baltaci","doi":"10.2174/0118715273374176250414051135","DOIUrl":"https://doi.org/10.2174/0118715273374176250414051135","url":null,"abstract":"<p><p>Brain ischemia-reperfusion injury (CIRI) refers to brain ischemia that leads to cellular dysfunction and cell death after a certain period, and ischemic damage is rescued by providing blood supply and reperfusion. And then, reperfusion includes components such as ion imbalance, mitochondrial dysfunction, oxidative stress, neuroinflammation, Ca2+ overload, and apoptosis, which do not cause tissue damage. Autophagy also occurs in CIRI due to oxygen deficiency, and autophagy has been shown to protect cells from ischemic injury. Flavonoids are a class of essential and diversified secondary plant metabolites found in different concentrations in leaves, flowers, roots, and fruits. Various studies have shown that flavonoids have healing qualifications such as anti-inflammatory, antimutagenic, anticarcinogenic, and antimicrobial. We aim to determine how flavonoids may affect signaling pathways and kinases in rats with CIRI. The results show that the activity of JAK2/STAT3, NF-κB, RhoA/ROCK, JNK-p38, and cAMKII signaling pathways increases under CIRI, and the PI3K/Akt/mTOR signaling pathway is suppressed. Studies using various flavonoids (kaempferol, chrysin, naringin, naringenin, quercetin, wogonin) have shown a neuroprotective effect by reversing the situation in signaling pathways during CIRI damage.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055148","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":"Cell-Free DNA, a Noninvasive Biomarker for Prediction and Detection of Neurodegenerative Diseases, New Insights, and Perspectives.","authors":"Tahere Barabadi, Elahe Sadat Mirjalili, Seyed Mahdi Mohamadi-Zarch, Hossein Rahimi, Fariborz Keshmirshekan, Seyyed Majid Bagheri","doi":"10.2174/0118715273366438250408120558","DOIUrl":"https://doi.org/10.2174/0118715273366438250408120558","url":null,"abstract":"<p><p>Neurodegenerative diseases pose serious threats to public health worldwide. Biomarkers for neurodegenerative disorders are essential to enhance the diagnostic process in clinical settings and to aid in the creation and assessment of effective disease-modifying treatments. In recent times, affordable and readily available blood-based biomarkers identifying the same neurodegenerative disease pathologies have been created, potentially transforming the diagnostic approach for these disorders worldwide. Emerging relevant biomarkers for α-synuclein pathology in Parkinson's disease include blood-based indicators of overall neurodegeneration and glial activation. Cell-free DNA (cfDNA), an encouraging non-invasive biomarker commonly utilized in oncology and pregnancy, has demonstrated significant potential in clinical uses for diagnosing neurodegenerative disorders. In this section, we explore the latest cfDNA studies related to neurodegenerative disorders. Moreover, we present a perspective on the possible role of cfDNA as a diagnostic, therapeutic, and prognostic indicator for neurodegenerative disorders. This review provides a summary of the most recent progress in biomarkers for neurodegenerative disorders such as Alzheimer's, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and traumatic brain injury.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999182","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":"Valproate Exposure as an In vitro Model for Studying Morpho-Molecular Features of ASD: A Systematic Review.","authors":"Quezia Damaris Jones Severino Vasconcelos, Michele Aramburu Serafini, Jaqueline Vieira Carletti, Gislei Frota Aragão, Carmem Gottfried, Victorio Bambini-Junior","doi":"10.2174/0118715273374315250417094713","DOIUrl":"https://doi.org/10.2174/0118715273374315250417094713","url":null,"abstract":"<p><strong>Background: </strong>Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a strong genetic and environmental basis. It frequently causes social and communication deficits, as well as repetitive behaviours. Valproic acid (VPA) has been shown to induce autisticlike features in animal models when administered during critical development periods. However, not much is known about its effect on cells to replicate ASD characteristics in vitro.</p><p><strong>Objective: </strong>This review explores in vitro VPA models to elucidate the molecular and morphological characteristics of ASD, emphasizing their potential and proposing directions for future research.</p><p><strong>Methods: </strong>PubMed, SciELO, Embase, Web of Science, and Scopus databases were searched, and 11 studies were included after screening.</p><p><strong>Results: </strong>The studies explored VPA's effects on various cell cultures, including human neural cell lines, primary adult neurons, and primary embryonic neurons. VPA was found to be neurotoxic in a dose- and time-dependent manner, with greater toxicity in immature and undifferentiated cells. In vitro, VPA can influence gene expression, increase oxidative stress, disrupt neurogenesis and synaptogenesis, affect the GABAergic system, and alter critical signaling pathways for brain development and cell differentiation, such as Wnt/β-catenin.</p><p><strong>Conclusion: </strong>In vitro models provide valuable insights into the morpho-molecular alterations induced by VPA and their connection to ASD. These findings highlight the need for further research into VPA's cellular effects to deepen our understanding of its role in ASD pathology.</p>","PeriodicalId":93947,"journal":{"name":"CNS & neurological disorders drug targets","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048762","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}