Cellular and Molecular Neurobiology最新文献

Kynurenine Pathway Modulation by Exercise in Multiple Sclerosis: Implications for Neuroprotection and Inflammation. 多发性硬化症运动对犬尿氨酸通路的调节：对神经保护和炎症的影响。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-22 DOI: 10.1007/s10571-025-01596-4

Rastegar Hoseini, Elnaz Ghafari

{"title":"Kynurenine Pathway Modulation by Exercise in Multiple Sclerosis: Implications for Neuroprotection and Inflammation.","authors":"Rastegar Hoseini, Elnaz Ghafari","doi":"10.1007/s10571-025-01596-4","DOIUrl":"https://doi.org/10.1007/s10571-025-01596-4","url":null,"abstract":"Multiple Sclerosis (MS) is a chronic, inflammatory, and neurodegenerative disease of the Central Nervous System (CNS) that is characterized by immune dysregulation and neuroinflammation. Owing to the generation of neuroactive metabolites, the kynurenine pathway (KP), one of the key pathways of tryptophan metabolism, influences the pathogenesis of MS by regulating immune responses and neuronal homeostasis. KP dysregulation results in the overproduction of neurotoxic metabolites such as quinolinic acid (QUIN), characterized by the loss of homeostasis between the neuroprotective (e.g., kynurenic acid, KYNA) and neurotoxic (e.g., QUIN) metabolites, contributing to neuroinflammation, excitotoxicity, and neurodegeneration. Recent evidence suggests that exercise may serve as a non-pharmacological intervention to modulate KP and limit MS progression. Both acute and chronic exercise, especially high-intensity interval training (HIIT), have been demonstrated to decrease the systemic levels of these neurotoxic KP metabolites and increase the neuroprotective KYNA production. Through the modulation of cytokine profiles toward an anti-inflammatory response and Aryl Hydrocarbon Receptor (AhR) activation that promotes immune tolerance, exercise is also an important regulator of the immune response. These findings imply that exercise normalizes KP homeostasis, decreases neuro-axonal damage and improves neuroprotection in MS, but the mechanisms of exercise-induced KP regulation as well as its long-term therapeutic role in MS treatment need further investigation. This review highlights the therapeutic potential of exercise as a complementary approach to existing drugs to ameliorate neuroinflammation and neurodegeneration in MS.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"74"},"PeriodicalIF":3.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications. 缺血性卒中中铁蛋白自噬与铁下垂之间的串扰：调节机制和治疗意义。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-20 DOI: 10.1007/s10571-025-01593-7

Zhanhua Shi, Kelong Chen, Yin Wang, Haixia Du

{"title":"The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications.","authors":"Zhanhua Shi, Kelong Chen, Yin Wang, Haixia Du","doi":"10.1007/s10571-025-01593-7","DOIUrl":"10.1007/s10571-025-01593-7","url":null,"abstract":"Ischemic stroke is a common cerebrovascular disease accompanied by a large number of neuronal death and severe functional impairment. In recent years, the role of ferroptosis and ferritinophagy in neuronal death after cerebral infarction has attracted great interest in the field of ischemic stroke. Ferroptosis is a newly discovered programmed cell death pattern characterized by iron overload, dysregulation of the xCT/GSH/GPX4 system, and lipid peroxidation system, which is closely associated with neurological damage after ischemic stroke. Ferritinophagy is a selective autophagy mediated by NCOA4 that regulates intracellular iron metabolism, and can be regulated by factors such as intracellular iron content and HERC2-FBXL5-IPR2 axis. Under normal physiological conditions, ferritinophagy maintains the balance of intracellular iron elements, and excessive activation can cause ferroptosis. Here, we mainly review the general mechanisms of ferroptosis and ferritinophagy, and focus on the relationship between ischemic stroke and ferroptosis/ferritinophagy. Specifically, we explored the crosstalk of ferroptosis and ferritinophagy in ischemic stroke and outlined current treatment strategies and key challenges. These observations may help to further understand the pathological events of ischemic stroke and bridge the gap between basic and translational research to provide novel insights for its treatment.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"73"},"PeriodicalIF":3.6,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667279","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}

引用次数: 0

Sex-Specific Neuropsychiatric Effects of Subanesthetic Ketamine Exposure in Pregnant Mice and Their Offspring. 亚麻醉氯胺酮暴露对怀孕小鼠及其后代的性别特异性神经精神影响。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-19 DOI: 10.1007/s10571-025-01582-w

Wei-Sheng Lin, Pei-Yu Wang, Sheng-Rong Yeh, Zoe Lai, Andrew Chengyu Lee, Shou-Zen Fan

{"title":"Sex-Specific Neuropsychiatric Effects of Subanesthetic Ketamine Exposure in Pregnant Mice and Their Offspring.","authors":"Wei-Sheng Lin, Pei-Yu Wang, Sheng-Rong Yeh, Zoe Lai, Andrew Chengyu Lee, Shou-Zen Fan","doi":"10.1007/s10571-025-01582-w","DOIUrl":"10.1007/s10571-025-01582-w","url":null,"abstract":"Depression during pregnancy is often overlooked and undertreated. Ketamine has been shown to exert prompt and sustained antidepressant effects in patients with depression, although concerns of potential neurotoxicity prohibit its use in pregnant women. Here, we aim to investigate the neurobehavioral effects of subanesthetic ketamine on pregnant mice and their offspring. We found that pregnant C57BL/6 mice receiving ketamine (10 mg/kg/day intraperitoneal) from gestation day 15 to 17 exhibited less depression-like behaviors. Prenatal ketamine treatment induced male-specific reduction in depression- and anxiety-like behaviors in adult offspring, without alterations in social and memory performance. These behavioral outcomes were associated with a male-specific increase in dendritic spine density of dentate gyrus granule cells, while neither dendritic architecture nor hippocampal neurogenesis was affected. N-methyl-D-aspartate receptor subunits GluN2A and GluN3A were expressed at significantly higher levels in the hippocampus of male as compared to female mouse embryos, suggesting sex-dependent actions of ketamine on developing brain. Overall, our study showed that prenatal exposure to subanesthetic ketamine could exert long-lasting neurobehavioral effects in a sex-dependent manner, with male offspring being more resilient to stress. These findings may have implications concerning ketamine use during pregnancy, and also provide clues about the developmental origins of emotional problems.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"72"},"PeriodicalIF":3.6,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667278","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}

引用次数: 0

MicroRNAs as Diagnostic Biomarkers of Myasthenia Gravis: A Systematic Review and Meta-Analysis. MicroRNAs作为重症肌无力的诊断性生物标志物：一项系统综述和荟萃分析。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-18 DOI: 10.1007/s10571-025-01585-7

Prayash Paudel, Asutosh Sah, Poonam Paudel

{"title":"MicroRNAs as Diagnostic Biomarkers of Myasthenia Gravis: A Systematic Review and Meta-Analysis.","authors":"Prayash Paudel, Asutosh Sah, Poonam Paudel","doi":"10.1007/s10571-025-01585-7","DOIUrl":"10.1007/s10571-025-01585-7","url":null,"abstract":"Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by fluctuating muscle weakness. MicroRNAs (miRNAs) have emerged as potential biomarkers for MG diagnosis, offering noninvasive and reliable detection. This systematic review and meta-analysis evaluated the diagnostic accuracy of miRNAs in MG. A comprehensive search of PubMed, Embase, and Google Scholar was conducted up to March 9, 2025. Eligible studies assessing miRNAs as MG biomarkers were selected on the basis of predefined criteria. Pooled sensitivity, specificity, and diagnostic odds ratios (DORs) were calculated via random effects model. Heterogeneity was assessed via I2, and publication bias was evaluated via Deeks' funnel plot. Nine studies including 1,797 participants were analysed. The pooled sensitivity and specificity were 0.80 (95% CI: 0.75-0.84) and 0.71 (95% CI: 0.65-0.77), respectively, with an area under the curve (AUC) of 0.83. Bivariate heterogeneity analysis indicated moderate variability, the cause of which were identified using subgroup analysis with region, clinical subtypes and seropositivity as subgroups. miRNAs demonstrate strong diagnostic potential for MG, with good sensitivity and specificity. However, standardized methodologies and further validation in large, multicentre studies is warranted.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"71"},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658541","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}

引用次数: 0

Targeting Neuronal Alpha7 Nicotinic Acetylcholine Receptor Upregulation in Age-Related Neurological Disorders. 靶向神经元α 7烟碱乙酰胆碱受体在年龄相关神经系统疾病中的上调

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-16 DOI: 10.1007/s10571-025-01586-6

Sharon Mariam Abraham, Sneha Suresh, Pragya Komal

{"title":"Targeting Neuronal Alpha7 Nicotinic Acetylcholine Receptor Upregulation in Age-Related Neurological Disorders.","authors":"Sharon Mariam Abraham, Sneha Suresh, Pragya Komal","doi":"10.1007/s10571-025-01586-6","DOIUrl":"10.1007/s10571-025-01586-6","url":null,"abstract":"The multifunctional roles of alpha7 nicotinic acetylcholine receptors (α7nAChRs), ranging from cognitive enhancement, neuroprotection, and anti-inflammatory action, credit tagging this receptor as \"unique\" among the cholinergic receptor family. The uniqueness of α7nAChRs in neuronal function and communication lies in their high calcium permeability among the cholinergic receptor family. The ionotropic function of α7nAChRs is governed by protein kinases' post-translational modification (PTMs), which alter their expression and function, affecting neuronal communication. A decrease in the ionotropic function of α7nAChRs and its downstream signaling pathways is observed across many neurologic disorders. The loss of α7nAChRs, decreased cholinergic function, and increased acetylcholinesterase levels are commonly associated with neuronal degeneration, cognitive impairment, and decreased memory function. An extensive body of evidence suggests the cognitive benefits of simple nutraceutical supplementation, Vitamin D3 (VD), in many neurologic disorders (Skv et al. in Mol Neurobiol 61:7211-7238, 2024). The present review will, however, focus on recent and past evidence deciphering the unique properties of α7nAChRs crucial for brain function. We have also emphasized on the therapeutic benefits of VD supplementation in restoring cholinergic neurotransmission and α7nAChRs expression in various neuropsychiatric and neurologic disorders.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"70"},"PeriodicalIF":3.6,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641934","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}

引用次数: 0

A Technical Assessment of a Commercial GFAP Lateral Flow Assay to Establish Proof-of-Concept for Use in Traumatic Brain Injury. 对商用GFAP侧流测定的技术评估，以建立用于创伤性脑损伤的概念验证。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-12 DOI: 10.1007/s10571-025-01594-6

Daniel P Whitehouse, Edward J Needham, Joshua D Bernstock, Edoardo Gaude, Liam Barrett, Soraya Ebrahimi, David K Menon, Virginia F J Newcombe

{"title":"A Technical Assessment of a Commercial GFAP Lateral Flow Assay to Establish Proof-of-Concept for Use in Traumatic Brain Injury.","authors":"Daniel P Whitehouse, Edward J Needham, Joshua D Bernstock, Edoardo Gaude, Liam Barrett, Soraya Ebrahimi, David K Menon, Virginia F J Newcombe","doi":"10.1007/s10571-025-01594-6","DOIUrl":"10.1007/s10571-025-01594-6","url":null,"abstract":"Glial fibrillary acidic protein (GFAP) is an emerging biomarker for the detection of acute intracranial pathology following acute brain injuries such as traumatic brain injury (TBI), stroke, and hypoxic-ischaemic encephalopathy. We undertake a proof-of-concept technical assessment of a commercial lateral flow test (LFT) for the detection of GFAP [the Upfront DX LVOne GFAP lateral flow assay (LFA)], against GFAP concentrations measured using a gold-standard assay [Single Molecule Arrays (Simoa®)-based Human Neurology 4-Plex B assay] in a TBI population. The ability of the LVOne GFAP LFA for identification of samples with GFAP concentrations above the manufacturer's reported lower limit of detection (≥ 0.2 ng/ml) was assessed, with further assessment of the association between the LVOne and a gold-standard assay made using Spearman's rank correlation coefficient and linear-mixed-effects modelling. Of the 50 samples, 39 had serum GFAP concentrations exceeding the reported lower limit of detection, with the LVOne GFAP LFA having a 95% (95% CI: 83%, 99%) sensitivity and a 64% (95% CI: 31%, 89%) specificity for detecting a serum GFAP concentrations over this lower limit. There was a significant positive correlation (Rho = 0.94, p < 0.001) between the Quanterix Simoa® GFAP level and the LVOne semiquantitative score, with a significant positive association seen using a linear-mixed-effects model (p < 0.001). In conclusion, the Upfront DX LVOne GFAP LFA is sensitive for the detection of elevated serum GFAP levels, and as such, may be a useful adjunct to the care of patients with acute brain injuries in the pre-hospital setting.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"69"},"PeriodicalIF":3.6,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12255627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616528","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}

引用次数: 0

The Role of Estrogen in Mitochondrial Disease. 雌激素在线粒体疾病中的作用。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-11 DOI: 10.1007/s10571-025-01592-8

Xi Huang, Cun-Hui Pan, Fei Yin, Jing Peng, Li Yang

引用次数: 0

Inhibition of P2Y6 Receptor-Mediated Microglia Phagocytosis Aggravates Brain Injury in Mice of Intracerebral Hemorrhage. 抑制P2Y6受体介导的小胶质细胞吞噬可加重脑出血小鼠脑损伤

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-08 DOI: 10.1007/s10571-025-01573-x

Ying Xu, Weiya Li, Jing Zhang, Weiwei Gao, Ting Zhang, Qing Chen, Nan Wang, Yongjia Zhou, Fengjiao Zhang, Jiahao Qin

{"title":"Inhibition of P2Y6 Receptor-Mediated Microglia Phagocytosis Aggravates Brain Injury in Mice of Intracerebral Hemorrhage.","authors":"Ying Xu, Weiya Li, Jing Zhang, Weiwei Gao, Ting Zhang, Qing Chen, Nan Wang, Yongjia Zhou, Fengjiao Zhang, Jiahao Qin","doi":"10.1007/s10571-025-01573-x","DOIUrl":"10.1007/s10571-025-01573-x","url":null,"abstract":"Intracerebral hemorrhage (ICH) is a devastating stroke subtype leading to severe sensorimotor dysfunction. Many studies showed that microglia phagocytosis could promote hematoma absorption, and scavenger receptors expressed on microglia were associated with its phagocytosis. As a specific phagocytic receptor, blocking the P2Y6 receptor (P2Y6R) with MRS2578 (3 mg/kg) could inhibit the phagocytic activity of microglia, which had been reported in a variety of neurological disorders, such as cerebral ischemia, Parkinson's diseases and neurodegenerative diseases. But the effects of P2Y6R-mediated microglia phagocytosis on the prognosis of ICH are still lacking. In the present study, we showed that P2Y6R expression elevated and peaked at day 3 after ICH. And treatment with MRS2578 (3 mg/kg) for three consecutive days could impair the phagocytosis of microglia, accompanied by delayed hematoma absorption rate, aggravated brain edema and blood-brain barrier disruption, as well as impaired neurological deficit in ICH mice. MRS2578 treatment also increased the expression of pro-inflammatory factors (TNF-α, iNOS) after ICH. Furthermore, MRS2578 treatment further increased the expression of NF-κB, which regulates the expression of these pro-inflammatory cytokines. In summary, our results suggested that regulating microglial phagocytosis could improve the prognosis of ICH, and P2Y6R offered a meaningful target.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"67"},"PeriodicalIF":3.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12238706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583215","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}

引用次数: 0

MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis. MiR-124和MiR-155作为多发性硬化症小胶质细胞介导炎症的治疗靶点。

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-07 DOI: 10.1007/s10571-025-01578-6

Elmira Roshani Asl, Seyedeh Elnaz Hosseini, Fatemeh Tahmasebi, Nadia Bolandi, Shirin Barati

{"title":"MiR-124 and MiR-155 as Therapeutic Targets in Microglia-Mediated Inflammation in Multiple Sclerosis.","authors":"Elmira Roshani Asl, Seyedeh Elnaz Hosseini, Fatemeh Tahmasebi, Nadia Bolandi, Shirin Barati","doi":"10.1007/s10571-025-01578-6","DOIUrl":"10.1007/s10571-025-01578-6","url":null,"abstract":"Multiple sclerosis (MS) is a chronic inflammatory disease associated with demyelination and microglial activation. Significant progress has recently been made in the development of strategies to treat MS with a focus on microglial cells. In response to injury, microglia, a population of mononuclear phagocytic cells, change from quiescent to activated. M1 microglia produce pro-inflammatory cytokines that cause additional injury, thus they are considered neurotoxic microglia. M2 microglia release anti-inflammatory factors that lead to the suppression of inflammatory responses; therefore, they have a neurotrophic phenotype. The balance between M1 and M2 phenotypes is important for nerve recovery. In neurodegenerative diseases, activated microglia are excessively shifted toward M1 or neurotoxic phenotype due to microRNA (miRNA) dysregulation. The miRNA as a class of non-coding RNAs, control the neuroinflammatory process by activation of microglia. The miR-124 is partly responsible for suppressing the neuroprotective and inflammatory processes by preventing microglia activation. Meanwhile, the microRNA 155, which is induced by pro-inflammatory agents in microglia, promotes the inflammatory process. Several studies have shown that in MS pathogenesis, miR-124 as an anti-inflammatory marker is significantly downregulated, while miR-155 shows an increase. In this study, we will investigate the role of miR-124 and miR-155 in the activation and alteration of microglial phenotype. Finding the relationship between microRNAs and glial cells and inflammation in MS may be used as a therapeutic method to reduce the symptoms in MS patients.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"63"},"PeriodicalIF":3.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574914","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}

引用次数: 0

Molecular Consequences of a Missense PHF21A Variant, c.1285G > A, Associated With Syndromic Neurodevelopmental Disorder. 与综合征性神经发育障碍相关的错义PHF21A变异c.1285G > a的分子后果

IF 3.6 4区医学

Cellular and Molecular Neurobiology Pub Date : 2025-07-07 DOI: 10.1007/s10571-025-01584-8

Cecilia M Gavilan, Yumie Murata-Nakamura, Robert Porter, Bradley Cutler, Sehj Rai, Hyung-Goo Kim, Shigeki Iwase

{"title":"Molecular Consequences of a Missense PHF21A Variant, c.1285G > A, Associated With Syndromic Neurodevelopmental Disorder.","authors":"Cecilia M Gavilan, Yumie Murata-Nakamura, Robert Porter, Bradley Cutler, Sehj Rai, Hyung-Goo Kim, Shigeki Iwase","doi":"10.1007/s10571-025-01584-8","DOIUrl":"10.1007/s10571-025-01584-8","url":null,"abstract":"PHF21A is a histone reader protein that recognizes unmethylated H3 lysine 4 and binds to DNA through its AT-hook motif. PHF21A heterozygosity is associated with intellectual disability, behavioral issues, and craniofacial dysmorphism, with or without seizures (IDDBCS), also known as PHF21A-related neurodevelopmental disorders. To date, the only missense variant associated with PHF21A-related disorders is c.1285G > A, which substitutes one of the core amino acids consisting of the AT-hook motif. This variant, located at the last nucleotide of exon 13, potentially disrupts both alternative splicing and the DNA binding function, providing a unique opportunity to investigate the molecular mechanisms underlying the disorders. Here, we systematically investigated the consequences of this variant on mRNA splicing and DNA binding. Our results indicate that the variant significantly reduced the splicing efficiency of PHF21A isoforms while maintaining DNA binding capability. Thus, reduced dosage rather than impaired DNA binding likely contributes to the cognitive impairments seen in the individual with this variant.","PeriodicalId":9742,"journal":{"name":"Cellular and Molecular Neurobiology","volume":"45 1","pages":"62"},"PeriodicalIF":3.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574915","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}

引用次数: 0