Journal of Molecular Neuroscience最新文献_第3页

Impaired Flow: Glymphatic Dysfunction in Ischemic Stroke and the Influence of Sex. 血流受损：缺血性脑卒中的淋巴功能障碍及性别的影响。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-07-04 DOI: 10.1007/s12031-025-02377-w

Khiany Mathias, Maiara de Aguiar da Costa, Victoria Linden de Rezende, Victor Duílio Antunes Maragno, Carlos Miguel Klima Felipe, Leyce da Rosa Dos Reis, Cinara Ludvig Gonçalves, Fabricia Petronilho

{"title":"Impaired Flow: Glymphatic Dysfunction in Ischemic Stroke and the Influence of Sex.","authors":"Khiany Mathias, Maiara de Aguiar da Costa, Victoria Linden de Rezende, Victor Duílio Antunes Maragno, Carlos Miguel Klima Felipe, Leyce da Rosa Dos Reis, Cinara Ludvig Gonçalves, Fabricia Petronilho","doi":"10.1007/s12031-025-02377-w","DOIUrl":"https://doi.org/10.1007/s12031-025-02377-w","url":null,"abstract":"The glymphatic system, essential for the clearance of metabolic waste from the brain, plays a complex role in the context of ischemic stroke (IS), influencing both the acute phase and long-term recovery. Following IS, impairment in cerebrospinal fluid (CSF) flow and in the clearance of neurotoxic substances, such as beta-amyloid and tau proteins, is observed. This dysfunction contributes to the accumulation of waste products in the brain parenchyma, increasing the risk of complications such as post-stroke dementia and depression. Several mechanisms are involved in this process, including perivascular space dilation, changes in aquaporin-4 expression and polarization, and the presence of reactive astrogliosis, all of which further compromise glymphatic function. These factors are also directly associated with the development of cerebral edema, a critical complication that exacerbates the severity of IS. Moreover, growing evidence suggests that biological sex may influence the glymphatic system's response to IS. Studies indicate that women may exhibit a more efficient glymphatic response, potentially mediated by hormones such as estrogen, which could offer greater protection against the deleterious effects of cerebral ischemia. However, further research is needed to confirm this hypothesis and to better understand the mechanisms underlying this sex-based difference. This review article aims to compile and critically discuss current evidence regarding the role of the glymphatic system in IS pathophysiology, also highlighting potential sex-related differences and their implications for future therapeutic approaches.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"85"},"PeriodicalIF":2.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564280","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

3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage. 3-苯氧苯甲酸诱导神经元戊烷素2上调补体活性并促进小胶质细胞介导的神经元突触损伤。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-26 DOI: 10.1007/s12031-025-02374-z

Guiling Hu, Kaidong Wang, Chenyang Wu, Qi Liu, Qianrong Zhang, Ai Qi, Min Huang

{"title":"3-Phenoxybenzoic Acid Induces Neuronal Pentraxin 2 to Upregulate Complement Activity and Promotes Microglia-Mediated Neuronal Synaptic Damage.","authors":"Guiling Hu, Kaidong Wang, Chenyang Wu, Qi Liu, Qianrong Zhang, Ai Qi, Min Huang","doi":"10.1007/s12031-025-02374-z","DOIUrl":"https://doi.org/10.1007/s12031-025-02374-z","url":null,"abstract":"3-Phenoxybenzoic acid (3-PBA) has been demonstrated to be associated with neurrotoxicity, however, the precise mechanism through which it exerts its neurotoxic effects remains to be fully elucidated. In this study, an investigation was conducted into the neuroimmunotoxicity of 3-PBA from an immunological perspective, with a combination of traditional toxicological methods and computer simulations being utilized in the research process. In vivo, 3-PBA has been shown to cause microstructural damage to early synapses in the mouse brain, which is widely accepted as the primary cause of cognitive dysfunction in mice. In vivo, it has been demonstrated that synaptic damage is induced by the upregulation of complement activity by neuronal pentraxin 2 (NP2), which in turn promotes microglia-mediated synaptic damage. Moreover, molecular docking simulations confirmed the interaction between 3-PBA and NP2. The present findings extend from a neurotoxicity perspective to 3-PBA-associated computer simulations, highlighting NP2 as a molecular initiating protein for 3-PBA-induced neurotoxicity. Additionally, the heightened complement activity downstream facilitated synaptic harm by microglia, causing a decrease in synaptic density and ensuing cognitive impairment. The outcomes of this study expand our knowledge of the neurotoxic nature of 3-PBA and supply hints and a theoretical foundation for evaluating its risks.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"83"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504429","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

Editorial: Scientists Should Be the Buffer of Turmoil. 社论：科学家应该成为动荡的缓冲器。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-23 DOI: 10.1007/s12031-025-02375-y

Noam Shomron

引用次数: 0

The Progress of Cognitive Dysfunction Impairment Caused by Temporal Lobe Epilepsy. 颞叶癫痫所致认知功能障碍的研究进展。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-21 DOI: 10.1007/s12031-025-02365-0

Qianqian Wang, Yanguang Geng, Xin Li, Yunhua Hao, Shuqi Huang

{"title":"The Progress of Cognitive Dysfunction Impairment Caused by Temporal Lobe Epilepsy.","authors":"Qianqian Wang, Yanguang Geng, Xin Li, Yunhua Hao, Shuqi Huang","doi":"10.1007/s12031-025-02365-0","DOIUrl":"10.1007/s12031-025-02365-0","url":null,"abstract":"Epilepsy is a chronic disease that is characterized primarily by seizures. One of the most common and detrimental comorbidities of epilepsy is cognitive impairment. Approximately, 30-40% of patients with chronic epilepsy experience cognitive impairment, which significantly impacts their daily functioning and quality of life and imposes a heavy burden on both patients and society. Numerous studies have established a correlation between epilepsy and cognitive impairment, showing that epilepsy patients exhibit varying degrees of cognitive deficits influenced by various factors. However, the clinical manifestations, underlying mechanisms, and influencing factors of cognitive impairment in epilepsy patients are still not fully understood. In this review, we aim to summarize and integrate the current understanding of the mechanisms underlying learning and memory impairments in temporal lobe epilepsy (TLE). We summarize the effects of abnormal neuronal discharges, synaptic plasticity alterations, neuroinflammation, and other potential contributors to cognitive dysfunction in TLE.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339744","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

More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use? 在发现PACAP的神经保护作用30多年后，是什么阻碍了它的临床应用？

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-21 DOI: 10.1007/s12031-025-02366-z

Asma Cherait, Xavier Xifró, Dora Reglodi, David Vaudry

{"title":"More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?","authors":"Asma Cherait, Xavier Xifró, Dora Reglodi, David Vaudry","doi":"10.1007/s12031-025-02366-z","DOIUrl":"10.1007/s12031-025-02366-z","url":null,"abstract":"Discovered in 1989, pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with strong neuroprotective properties, as shown in various neurodegenerative preclinical models of Parkinson, Alzheimer, or Huntington diseases. PACAP neuroprotection has also been reported in animal models of cerebral ischemia and traumatic brain injury. The neuroprotective effect of PACAP occurs through its capacity to modulate most of the multiphasic aspects of neuronal diseases, such as oxidative stress, neuronal cell death, and inflammation. However, more than three decades after its discovery, and although PACAP neurotrophic and neuroprotective activities have now been largely documented, its clinical use is still awaited. Thus, the aim of this manuscript is to discuss the main reasons which limit the use of PACAP as a therapeutic agent for the treatment of neuronal diseases. To achieve this objective, an opinion survey has been conducted among experts in the field of PACAP, and a bibliographic investigation was carried out.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"80"},"PeriodicalIF":2.8,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339743","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

Cerebrospinal Fluid-Derived Genomic Alterations Tracking Glioma. 脑脊液衍生的基因组改变追踪神经胶质瘤。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-20 DOI: 10.1007/s12031-025-02361-4

Zhongyuan Zhu, Yanjiao Yu, Fuzhong Liu, Xiaosong Yang, Zijie Zhou, Zhengquan Zhu, Zifeng Wang, Ji Zhang

{"title":"Cerebrospinal Fluid-Derived Genomic Alterations Tracking Glioma.","authors":"Zhongyuan Zhu, Yanjiao Yu, Fuzhong Liu, Xiaosong Yang, Zijie Zhou, Zhengquan Zhu, Zifeng Wang, Ji Zhang","doi":"10.1007/s12031-025-02361-4","DOIUrl":"10.1007/s12031-025-02361-4","url":null,"abstract":"Diffuse gliomas are aggressive brain tumors known for heterogeneity and frequent oncogenic mutations. Our study harnessed circulating tumor DNA (ctDNA) in cerebrospinal fluid (CSF) as a less invasive method for disease monitoring and guiding therapeutic interventions. Through targeted sequencing of ctDNA from CSF and matched blood and tumor tissue samples, we aimed to identify glioma-associated somatic alterations and DNA fragmentations. The identified glioma-associated mutations from ctDNA in CSF and genome DNA of the resected tumor were compared, revealed a broad genetic alteration spectrum within CSF ctDNA, closely reflecting the genomic profiles of corresponding tumor samples. And we found 91.67% (11/12) of tissue samples analyzed by next-generation sequencing (NGS), a minimum of one tumor-specific mutation was present. Also, at least one tumor-specific mutation was detected in 91.67% of serial CSF ctDNA samples (11/12). In some patients, CSF sequencing showed higher mutation detection rate compared to tissue sequencing. Moreover, the average mutation frequencies were similar between CSF and tumor tissue samples. These results support that CSF ctDNA is a reliable candidate for detecting glioma-specific alterations for molecular profiling, complements the histopathological, molecular and imaging defect, and can be adopted into clinical practice.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"79"},"PeriodicalIF":2.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332236","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 Astrocyte Elevated Gene- 1 Expression and other Risk Factors for Different Varieties of Diabetic Optic Neuropathy in Egyptian Patients with Diabetic Retinopathy. 埃及糖尿病视网膜病变患者不同类型糖尿病视神经病变星形胶质细胞基因- 1表达升高及其他危险因素

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-19 DOI: 10.1007/s12031-025-02372-1

Noha Rabie Bayomy, Sameh Mohamed Elgouhary, Eman Masoud Abd El Gayed, Karema Abdelhady Diab, Mai A Kamel, Nashwa Mahmoud Mouhamed Muharram

{"title":"The Astrocyte Elevated Gene- 1 Expression and other Risk Factors for Different Varieties of Diabetic Optic Neuropathy in Egyptian Patients with Diabetic Retinopathy.","authors":"Noha Rabie Bayomy, Sameh Mohamed Elgouhary, Eman Masoud Abd El Gayed, Karema Abdelhady Diab, Mai A Kamel, Nashwa Mahmoud Mouhamed Muharram","doi":"10.1007/s12031-025-02372-1","DOIUrl":"10.1007/s12031-025-02372-1","url":null,"abstract":"To assess the role of the mRNA and protein expression of Astrocyte Elevated Gene- 1 (AEG-1) and other possible risk factors for diabetic optic neuropathy (DON) in Egyptian patients with diabetic retinopathy (DR). This case-control study constituted 450 diabetic patients divided into three groups: Group 1 included 150 DR patients with any sign of DON (diabetic papillopathy (DP), non-arteritic anterior ischemic optic neuropathy (AION), and optic atrophy (OA)). Group 2 included 150 DR patients without any sign of DON. Group 3 included 150 sex and age-matched diabetic patients without any sign of DR or DON. The expression level of AEG-1 mRNA was assessed by real-time PCR. Serum AEG-1 was determined by ELISA. Multivariate logistic regression analysis was conducted to assess the DON risk factors. The mRNA expression of the AEG-1 gene and AEG-1 protein levels were significantly increased (P < 0.001) in diabetic patients with (group 1) than without (group 2) DON. ROC curve analysis showed that the mRNA level of the AEG-1 gene exhibited a 70% specificity and a 79.33% diagnostic sensitivity. The diagnostic sensitivity of the serum concentration of AEG-1 was 84.67%, while the specificity was 70%. Multivariate regression analysis showed that the risk factors for DON were 2hpp blood sugar, HbA1c, serum cholesterol, AEG-1 gene's mRNA expression, and AEG-1 protein. Serum cholesterol, the AEG-1 gene's mRNA expression, and the AEG-1 protein are risk factors for all varieties of DON. While the blood glucose levels favour the development of DP, control of diabetes favours the occurrence of AION. Lastly, diabetes duration is more related to the presence of OA.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 3","pages":"78"},"PeriodicalIF":2.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12178977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332237","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

Ferroptosis: Disease Associations and Therapeutic Target Exploration. 上睑下垂：疾病关联及治疗靶点探索。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-14 DOI: 10.1007/s12031-025-02369-w

Hailing Wang, Liwei Jia, Rui Yin, Shujun Xu, Xin Meng

{"title":"Ferroptosis: Disease Associations and Therapeutic Target Exploration.","authors":"Hailing Wang, Liwei Jia, Rui Yin, Shujun Xu, Xin Meng","doi":"10.1007/s12031-025-02369-w","DOIUrl":"10.1007/s12031-025-02369-w","url":null,"abstract":"Ferroptosis, a distinct form of cell death, is transforming the understanding of complex diseases such as cancer, neurodegenerative disorders. Driven by iron accumulation and lipid peroxidation, ferroptosis offers significant therapeutic potential by selectively targeting diseased cells. Ferroptosis is closely associated with renal impairment, metabolic disease, and neurological disorders. The current focus is on understanding the signaling pathways of ferroptosis to precisely regulate the ferroptosis mechanism. For example, ferroptosis increases intracellular selenium content and synergistically activates transcription factors transcription factor AP-2 gamma and specificity protein 1 to promote glutathione peroxidase-4 expression (GPX4). Despite its broad therapeutic potential, significant challenges remain, particularly in uncovering the detailed molecular mechanisms of ferroptosis and minimizing off-target effects. However, in the past two years, there has been a few comprehensive reviews on the exploration of therapeutic targets related to ferroptosis in disease treatment. This article provides a summary of the current understanding of ferroptosis mechanisms, its links to various diseases, and the exploration of potential therapeutic targets. By elucidating the complex molecular pathways of ferroptosis and highlighting its role in disease progression, we gain new insights for potential therapeutic strategies. This underscores the substantial theoretical significance of targeting ferroptosis for treatment purposes.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":"76"},"PeriodicalIF":2.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293081","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

Salicylaldehyde Benzoylhydrazone Protects Against Ferroptosis in Models of Neurotoxicity and Behavioural Dysfunction, In Vitro and In Vivo. 水杨醛苯甲酰腙在体外和体内对神经毒性和行为功能障碍模型的铁下垂有保护作用。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-14 DOI: 10.1007/s12031-025-02371-2

Niamh C Clarke, Ellen McCabe, Lasse D Jensen, Bernadette S Creaven, Derek A Costello

{"title":"Salicylaldehyde Benzoylhydrazone Protects Against Ferroptosis in Models of Neurotoxicity and Behavioural Dysfunction, In Vitro and In Vivo.","authors":"Niamh C Clarke, Ellen McCabe, Lasse D Jensen, Bernadette S Creaven, Derek A Costello","doi":"10.1007/s12031-025-02371-2","DOIUrl":"10.1007/s12031-025-02371-2","url":null,"abstract":"Metal dyshomeostasis in the brain is a key feature of many neuropathologies, including hypoxic and traumatic injury and chronic conditions such as Alzheimer's and Parkinson's disease. Ferroptosis is a form of cell death driven by the intracellular accumulation of iron. This is primarily characterised by a loss in endogenous antioxidant capacity and uncontrolled lipid peroxidation. Ferroptosis has been reported to underlie the pathology associated with several neurological and neurodegenerative conditions and has, therefore, become an attractive target for therapeutic intervention. Salicylaldehyde benzoylhydrazone (SBH) is a specialised hydrazone agent, known for its antibacterial and anticancer properties. It has robust metal-chelating capacity, with a particular affinity for complexing with iron and copper. The current study sought to investigate the potential of SBH to act as an anti-ferroptotic agent and to alleviate the neurotoxic and dysfunctional consequences of iron overload. We demonstrate that SBH can alleviate the death of HT22 hippocampal neurons, induced by exposure to the iron donor, ferric ammonium citrate (FAC). This was accompanied by a reduction in intracellular iron and lipid peroxidation, and alleviation of hallmark changes in gene expression indicative of ferroptosis. Using FAC-incubated zebrafish larvae as an in vivo model of iron overload, we reveal that SBH can reduce the mortality and toxicity associated with FAC exposure. Moreover, we report a FAC-mediated dysfunction in intrinsic sensorimotor reflex behaviour, which is restored by SBH. Taken together, our findings highlight SBH as an anti-ferroptotic agent and support its further investigation as a potential neurotherapeutic for conditions associated with iron dysregulation.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":"77"},"PeriodicalIF":2.8,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293082","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

Drp1-Mediated Mitochondrial Fission Is Essential for Chemical-Induced Neuronal Transdifferentiation from Human Primary Fibroblasts. drp1介导的线粒体分裂对化学诱导的人原代成纤维细胞的神经元转分化至关重要。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2025-06-13 DOI: 10.1007/s12031-025-02367-y

Jijuan Yang, Chun Li, Chunhua Wang, Xuemei Wang, Jiaqi Liu, Nan Yu, Wenqing Du, Shuhong Chi

{"title":"Drp1-Mediated Mitochondrial Fission Is Essential for Chemical-Induced Neuronal Transdifferentiation from Human Primary Fibroblasts.","authors":"Jijuan Yang, Chun Li, Chunhua Wang, Xuemei Wang, Jiaqi Liu, Nan Yu, Wenqing Du, Shuhong Chi","doi":"10.1007/s12031-025-02367-y","DOIUrl":"10.1007/s12031-025-02367-y","url":null,"abstract":"Neuronal replacement therapy recently holds promise for neurodegenerative disease treatment. Somatic cell-derived neurons are the main cell source for this therapy; however, the induction mechanisms remain to be fully elucidated. Emerging evidence indicates that mitochondrial architecture undergoes substantial remodeling throughout cellular reprogramming processes. To explore the implications of mitochondrial dynamics in chemical-induced neuronal transdifferentiation, human foreskin fibroblasts (HFFs) were directly reprogrammed into functional neurons with our previously developed small molecule compound. The results showed that the mitochondrial morphology of HFFs shifted from tubular and reticular to fragmented shapes at an early stage of induced neurulation. Concurrently, gene and protein expression levels of the mitochondrial fission protein Drp1 was significantly increased in HFFs after induction. Both Drp1-specific siRNA and Drp1-GTPase inhibitor mdivi-1 treatment significantly attenuated the neuronal transdifferentiation of HFFs to neurons respectively, which can be attributed to the modulation of mitochondrial dynamics toward a fusion-dominant state through Drp1 suppression. Collectively, our experimental findings establish Drp1-dependent mitochondrial fission as a critical early requirement in the chemical reprogramming cascade that facilitates HFF transdifferentiation into neuronal lineages. Targeting Drp1 may enhance the efficiency of neuronal transdifferentiation, thereby providing sufficient therapeutically relevant neurons for neurodegenerative disease treatment.","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 2","pages":"75"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144281903","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