Cellular and Molecular Neurobiology最新文献

{"title":"The Role and Diagnostic Efficacy of the METTL14/GADD45B m⁶A Methylation/BDNF Regulatory Axis in Acute Ischemic Stroke.","authors":"Jin-Ying Lai, Jun-Hua Lu, Meng-Yue Li, Bei-Bei Li, Bao-Yun Jin, Jiang-Jie Hao, Ying Zhao, Ying Lin, Li-Qiu Ma, Ren Liu, Shu-Fan Zhang, Hong-Jun Guan","doi":"10.1007/s10571-026-01710-0","DOIUrl":"10.1007/s10571-026-01710-0","url":null,"abstract":"<p><p>Despite advances in acute ischemic stroke (AIS) research, identifying reliable biomarkers and regulatory mechanisms remains challenging. We first identified AIS-related genes via extensive literature review, retrieved dataset GSE16561 from the Gene Expression Omnibus (GEO, https://ncbi.nlm.nih.gov/geo/ ), and performed differential/enrichment analyses. Bioinformatics verified N6-methyladenosine (m⁶A) sites in target genes, focusing on the methyltransferase-like protein 14 (METTL14)/growth arrest and DNA damage-inducible β (GADD45B) m⁶A methylation/brain-derived neurotrophic factor (BDNF) axis. Peripheral blood samples, biochemical indicators, and demographic data were collected from Hongqi Hospital Affiliated to Mudanjiang Medical University. Human umbilical vein endothelial cells (HUVECs) underwent transfection and oxygen-glucose deprivation (OGD). METTL14, GADD45B, and BDNF were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR); BDNF protein by enzyme-linked immunosorbent assay (ELISA); global RNA m⁶A by Dot Blot; and GADD45B m⁶A by methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-qPCR). Differential, diagnostic efficacy, logistic regression analyses, and nomogram validation were conducted. AIS patients showed increased METTL14, decreased GADD45B/BDNF, and increased levels of global m⁶A RNA and GADD45B m⁶A mRNA (P < 0.05). Receiver operating characteristic (ROC) analysis confirmed the three genes' good diagnostic efficacy. The nomogram integrating these genes, globulin (GLOB), diabetes, high-density lipoprotein cholesterol (HDL-C), and hypertension performed excellently. This study highlights METTL14, GADD45B, and BDNF as key AIS biomarkers; METTL14 may indirectly regulate BDNF via GADD45B m⁶A methylation, providing potential therapeutic targets and novel mechanistic insights.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13385536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unknotting the Role of circRNAs and IGF2BP3 in Alzheimer's Disease.","authors":"Sayed Mohammad Firdous, Sinhapurage Navodi Sandamini Jayathilaka, Souvik Marick, Pratyush Porel","doi":"10.1007/s10571-026-01724-8","DOIUrl":"10.1007/s10571-026-01724-8","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a complex neurological ailment that is associated with memory loss, confusion, and mood disturbances. Genetic, molecular, and cellular factors, including oxidative stress, inflammation, neurotransmitter alterations, and amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), are associated with the disease. These can be associated with protein and DNA damage, mitochondrial dysfunction, energy shortages, inflammation, and hippocampal neuron death. Circular non-coding RNAs (circRNAs) are covalently closed and essential to many physiological and pathological processes. CircRNA may be a molecular modulator of neurodegeneration, as it may influence protein transcription and interaction with essential RNA-binding proteins (RBP) in the cortical and hippocampal regions, particularly in photoreceptor neurons and white matter.Insulin-like Growth Factor 2 mRNA-Binding Protein 3. (IGF2BP3), which belongs totheinsulin-like growth factor 2 encoded mRNA-binding protein family, affects neuronal differentiation, synaptic plasticity, translation, localization, mRNA stability, and neurogenesis. Research indicates that IGF2BP3 has been reported to modulate neuron survival and function genes, as well as BACE1 translation, which creates Aβ. AD has a complex etiology; thus, understanding its molecular processes is crucial. Investigating circRNAs and IGF2BP3 activities may reveal new disease are associated with and therapy options. This review explores the emerging roles ofcircRNAs as diagnostic biomarkers and potential therapeutic targets inmanagingAD.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13201729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between CDH1 Downregulation and Lymphocyte Cell-Cycle Dysfunction in Alzheimer's Disease and Mild Cognitive Impairment.","authors":"Paloma Monllor, Begoña Lopez, Maria-Angeles Lloret, Jose-Luis Leon, Erika Lopez, Mari-Carmen Badia, Ana Lloret","doi":"10.1007/s10571-026-01725-7","DOIUrl":"10.1007/s10571-026-01725-7","url":null,"abstract":"<p><p>Alzheimer’s disease (AD) is characterized by the intracellular accumulation of amyloid-β and tau pathology, which disrupt multiple cellular regulatory pathways, including those involved in cell cycle control. Dysregulation of the anaphase-promoting complex/cyclosome (APC/C), particularly through altered expression of its coactivator CDH1, has been implicated in neuronal dysfunction in AD. Beyond the central nervous system, increasing evidence suggests that peripheral immune cells also exhibit functional alterations associated with the disease. In this study, we recruited patients with mild cognitive impairment (MCI) and AD, along with non-demented controls. We isolated T lymphocytes to assess mitogen-induced lymphocyte proliferation and associated molecular changes. We report that lymphocytes from MCI and AD patients show a reduced proliferative response compared to controls, accompanied by decreased CDH1 mRNA expression and altered expression of APC/C-related genes. These changes were associated with markers of oxidative stress and cellular stress pathways. Together, our findings identify an association between reduced CDH1 expression and impaired lymphocyte proliferation in AD and MCI, supporting the relevance of peripheral immune cells as candidates for systemic markers of disease-related cellular dysfunction.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Inhibition of Ferroptosis Alleviates Early Brain Injury After Subarachnoid Hemorrhage In Vitro and In Vivo via Reduction of Lipid Peroxidation.","authors":"Yuchen Li, Yao Liu, Pei Wu, Yang Tian, Binbing Liu, Jinju Wang, Ji Bihl, Huaizhang Shi","doi":"10.1007/s10571-026-01727-5","DOIUrl":"10.1007/s10571-026-01727-5","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MELK is Required for G2/M Phase Progression in Cortical Progenitors: Insights from Rare ASD-Associated Variants.","authors":"Liyang Zhao, Xianjing Li, Kang Yang, Miaomiao Jiang, Zhonghe Chen, Yiqian Shao, Tianlan Lu, Dai Zhang, Lifang Wang, Jun Li","doi":"10.1007/s10571-026-01728-4","DOIUrl":"10.1007/s10571-026-01728-4","url":null,"abstract":"<p><p>Maternal embryonic leucine zipper kinase (MELK) is a cell cycle regulator, yet its role in embryonic cortical development remains unclear. We identified ultra-rare, predicted loss-of-function MELK variants in ASD individuals, prompting this functional investigation. Published human single-cell transcriptomics showed that MELK expression is enriched in neural progenitors and correlates with the G2/M phase. Using in utero electroporation in mouse cortex, we found that Melk knockdown reduced the proportion of progenitors in G2/M phase. Knockdown also caused impaired multipolar-to-bipolar transition and shorter leading processes. Complementing these findings, transcriptomic analysis of FACS-sorted Melk-knockdown cortical cells revealed downregulation of G2/M-related genes and cytoskeletal regulators linked to neuronal morphogenesis. Together, these findings identify MELK as a critical regulator of both G2/M phase progression and neuronal morphogenesis during cortical development, providing a mechanistic link to neurodevelopmental conditions.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Enriched Environment Improve Chronic Immobilization Stress-Induced Cognitive and Behavioral Changes in Adult Male Rats?","authors":"Mona A Mohammed, Amira S Ahmed, Fatma M M Salem, Eman S H Abd Allah","doi":"10.1007/s10571-026-01712-y","DOIUrl":"10.1007/s10571-026-01712-y","url":null,"abstract":"<p><p>Chronic stress induces detrimental effects on cognition, behavior, and hippocampal integrity. An enriched environment (EE) has been shown to enhance learning and memory; however, its role against chronic immobilization stress (CIS)-induced alterations and the underlying mechanisms remain insufficiently explored. This study aimed to investigate the protective effects of EE on CIS-induced behavioral, molecular, and structural changes in the hippocampus of adult male rats. Thirty-two adult male Wistar albino rats were assigned to four groups: control, control + EE, CIS, and CIS + EE. Rats were subjected to CIS (4 h/day) followed by EE exposure (2 h/day) for 28 days. Behavioral assessments were conducted. Serum corticosterone levels, hippocampal brain-derived neurotrophic factor (BDNF), and mRNA expression of aquaporin-4 (AQP4) and glutamate receptors (GluA1 and GluA2) were evaluated. Histopathological, ultrastructural, and immunohistochemical (LC3) examinations were performed. EE significantly ameliorated CIS-induced cognitive and behavioral impairments and restored hippocampal histological and ultrastructural integrity. These effects were associated with reduced serum corticosterone levels, increased hippocampal BDNF levels, and upregulated expression of AQP4, GluA1, and GluA2 mRNA. These findings suggest that EE is a promising non-pharmacological strategy for mitigating stress-induced hippocampal dysfunction and cognitive decline.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13076856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell Therapy for Spinal Cord Injury: Mechanistic Insights and Translational Challenges.","authors":"Duc-Hiep Bach, Bui Van Giang, Thanh Liem Nguyen","doi":"10.1007/s10571-026-01720-y","DOIUrl":"10.1007/s10571-026-01720-y","url":null,"abstract":"<p><p>Spinal cord injury (SCI) causes devastating and permanent neurological disability, with no restorative treatments currently available. Cell-based therapies have long been regarded as the most promising regenerative strategy, demonstrating robust functional improvement in preclinical models. However, clinical outcomes have been inconsistent, exposing a persistent translational gap. This review critically appraises leading cell therapy platforms, ranging from mesenchymal and neural stem cells to next-generation engineered tissues. We dissect the molecular mechanisms underlying therapeutic efficacy and analyze key translational barriers, including GMP manufacturing, potency assay development, and clinical trial design. Integrating lessons from past failures with emerging advances in imaging biomarkers and immune-microenvironment modulation, we propose a strategic roadmap framed by a “renovate-and-rebuild” paradigm. We identify timing-by-mechanism mismatches and inadequate scar remodeling as central drivers of variable efficacy, and introduce a biomarker-gated indication algorithm to align therapies with lesion biology. Collectively, these insights argue for reframing SCI repair as a staged, biology-matched process rather than a single-shot intervention.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Symbiosis and Vulnerability in the CNS Axon-Myelin Unit.","authors":"Kun Miao, Meng Meng, Liangjing Liu, Meiyu Li, Yuanyuan Bai, Ying Guo, Guohui Zhang, Jiming Kong, Jiao Mu","doi":"10.1007/s10571-026-01729-3","DOIUrl":"10.1007/s10571-026-01729-3","url":null,"abstract":"<p><p>Axonal degeneration and demyelination are common pathological phenotypes in central nervous system (CNS) injury and degenerative diseases. Axonal and myelin diseases have generally been considered distinct phenomena, although our knowledge of why the axon-myelin unit (AMU), as a highly interconnected structure, serves as a common point of vulnerability to damage remains inadequate. In this review, we first reaffirm that the tight biological interconnections between axons and myelin should be recognized as a \"symbiotic\" unit across development, metabolism, and disease progression. Second, we systematically delineate the fundamental structural architecture and metabolic coupling of AMU. Third, we analyze how the impairment of one component of AMU influences the survival and functional integrity of others. In conclusion, we present a unique conceptual framework indicating that therapeutic methods targeting bioenergetic support in the CNS should concentrate on the energy coupling pathways and damage-crossover mechanisms of the AMU.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13184064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Association of Genetic Determinants of SIRT1, MTHFR, and MIR146A Gene Polymorphism with the Ischemic Stroke Predisposition: A Case Control Study.","authors":"Abdullah Hamadi, Rashid Mir, Osama M Al-Amer, Mohammed Alasseiri, Mamdoh S Moawadh, Jameel Barnawi, Mohammad A Alanazi, Atif Abdulwahab A Oyouni, Abeer Al-Tuwaijri, Fawzyah Obeedallah Albaldi, Hassan A Madkhali","doi":"10.1007/s10571-026-01688-9","DOIUrl":"10.1007/s10571-026-01688-9","url":null,"abstract":"<p><p>Stroke is a major cause of disability and the second greatest cause of death. Both acute and chronic strokes have few available treatment options. Nonetheless, the technique known as genome-wide association study (GWAS) is beginning to significantly influence our comprehension of the genetics of stroke. Therefore, the objective of the present study was to examine the associations between Sirtuin-1 (SIRT1), Methylenetetrahydrofolate reductase (MTHFR), and microRNA 146a (MIR146A) gene variations with ischemic stroke (IS) risk. The study included 200 participants: 100 with clinically confirmed IS and 100 healthy controls. Genotyping of SIRT1 (rs7069102), MTHFR (rs1801131), and MIR146A (rs2910164) was performed using the Amplification-Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR). Blood biochemistry, including lipid profiles and glycemic markers, was determined using spectrophotometric enzymatic colorimetric assays. Statistical techniques employed included the Chi-square test, Fisher’s exact test, and multivariate logistic regression analysis to determine Odds Ratios (OR) and 95% Confidence Intervals (CI). In the codominant model, heterozygosity for MIR146A GC (OR = 1.97, P = 0.040), SIRT1 GC (OR = 1.84, P = 0.044), and MTHFR AC (OR = 2.55, P = 0.0019) was significantly associated with increased stroke susceptibility. In the dominant model, MIR146A (GC + CC), SIRT1 (GC + CC), and MTHFR (AC + CC) genotypes were strongly associated with increased risk (P < 0.05). In the recessive model, MIR146A CC and MTHFR CC genotypes were significantly associated with stroke risk, whereas the SIRT1 CC genotype did not reach statistical significance (P = 0.065). Allelic comparison revealed that the C alleles of MIR146A, SIRT1, and MTHFR were all strongly associated with stroke predisposition (P < 0.05). We conclude that there is a possible strong association between the SIRT1 rs7069102 C > G, MTHFR rs1801131 C > A and MIR146A rs2910164 C > G gene variants and ischemic stroke susceptibility. To the best of our knowledge, it is the first study to highlight the association between these genetic variations and the predisposition of stroke in our populations. Large-scale case–control studies in the future are required to confirm these results. These results, when confirmed, can be used in genetic testing for the screening and prognosis of stroke.</p>","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Mitochondrial Transplantation Therapy for Ischemic Stroke: Progress and Challenges.","authors":"Zhi-Hong Zhao, Xue-Ling Yang, Zi-Wei Lu, Tao Li, Li-Li Zhao, Ye Li, Mei-Juan Dang, Gui-Lian Zhang, Kun Chen, Hong Fan","doi":"10.1007/s10571-026-01721-x","DOIUrl":"10.1007/s10571-026-01721-x","url":null,"abstract":"","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"46 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}