Molecular Neurobiology最新文献

{"title":"Oxytocin Regulated Neuroinflammation through OTR/Mitochondria Mediated Pathway to Improve Hypoxia-Induced Brain Injury.","authors":"Xiaomei Yang, Kai Li, Lin Chen, Lei Wang, Xuyang Wang, Kangping Lu, Yu Bai, Yonghao Hou, Jingchen Hou, Chao Wang, Xiaoyan Cheng, Joseph Oldam, Jingui Yu, Jianbo Wu, Baozhu Sun","doi":"10.1007/s12035-025-05061-7","DOIUrl":"https://doi.org/10.1007/s12035-025-05061-7","url":null,"abstract":"<p><p>Neonatal hypoxic-ischemic encephalopathy, a severe consequence of birth asphyxia, remains a leading cause of newborn mortality and permanent neurological disabilities worldwide. The limited therapeutic options and incomplete understanding of its pathological mechanisms present significant challenges in clinical management. This study aimed to investigate the therapeutic effects of oxytocin on hypoxic brain injury and elucidate its underlying molecular mechanisms. Five-day-old C57BL/6 mice were subjected to hypoxia (10% oxygen) for 7 days, with or without oxytocin treatment (0.1 mg/kg, i.p., every other day). Brain sections were examined by H&E and Nissl staining, TUNEL assay, and immunofluorescence. Western blot and real-time PCR were performed to analyze protein expression and mitochondrial DNA content in cortical tissues. OT treatment attenuated hypoxia-induced brain injury, as evidenced by improved histological outcomes in H&E and Nissl staining. OT significantly reduced neuronal apoptosis shown by TUNEL staining and decreased cleaved-caspase3 expression in cortical tissues. Furthermore, OT maintained mitochondrial homeostasis by regulating fusion-fission dynamics and mtDNA content. OT also suppressed microglial activation and neuroinflammation through downregulating NF-κB signaling and NLRP3 inflammasome. These protective effects were partially reversed by the OTR antagonist Cligosiban. Our findings demonstrate that OT protects against hypoxic neonatal brain injury via OTR signaling, which maintains mitochondrial homeostasis and prevents neuronal apoptosis and neuroinflammation. This study provides experimental evidence for OT as a potential therapeutic agent in treating hypoxic brain injury.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Regulation of Amyloid production in Alzheimer's Disease via Curcumin-Loaded Silver Nanoparticles with Antioxidant and Acetylcholinesterase-Inhibiting Properties.","authors":"Seyedeh Zahra Malek, Amir Arasteh","doi":"10.1007/s12035-025-05125-8","DOIUrl":"https://doi.org/10.1007/s12035-025-05125-8","url":null,"abstract":"<p><p>This study investigates the phytochemical composition, antioxidant activity, and anti-Alzheimer effects of curcumin used in the green synthesis of silver nanoparticles (curcumin-Ag NPs). The synthesis process and nanoparticle characteristics were thoroughly examined using UV-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The resulting nanoparticles exhibited a particle size between 50 and 100 nm with a zeta potential of - 33 mV, indicating colloidal stability. FTIR spectra showed characteristic peaks at 3537, 1627, 1509, and 1278 cm^-1, corresponding to phenolic hydroxyl groups, C = O, and CH groups, confirming the presence of curcumin on the nanoparticle surface. SEM imaging revealed spherical nanoparticles with sizes ranging from 61 to 78 nm, and EDX analysis confirmed the presence of silver with characteristic peaks at approximately 3 keV. XRD patterns demonstrated that the nanoparticles possess a crystalline structure. Antioxidant activity assessed via DPPH assay increased with concentration, with an IC₅₀ value of 1167.9 µg/ml. Anti-Alzheimer effects were observed at lower concentrations, with up to 44.3% inhibition of acetylcholinesterase activity at 585 µg/ml. Notably, the dual properties of antioxidant and enzyme inhibitory effects highlight the potential of curcumin-Ag NPs as multifunctional agents for neurodegenerative diseases. This work offers new insights into the green synthesis of bioactive nanoparticles and their therapeutic prospects against Alzheimer's disease.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Panax Ginseng Protects Against Doxorubicin-Induced Testicular Injury in Male Rats by Modulating NF-κB/COX-2 and AR Pathways.","authors":"Yesim Yeni, Betul Cicek, Ahmet Hacimuftuoglu, Mustafa Ozkaraca, Behzad Mokhtare","doi":"10.1007/s12035-025-05116-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05116-9","url":null,"abstract":"<p><p>Panax ginseng (PG) is a medicinal plant used for many years to treat many diseases. The current study aimed to investigate the possible prophylactic and therapeutic effects of PG extract on doxorubicin (DOX)-induced testicular toxicity in rats. 32 adult male Sprague-Dawley rats (200-250 g) were used in the experiment. The experimental groups were designed as control (normal saline, intraperitoneal), DOX (18 mg/kg, intraperitoneal), PG (200 mg/kg, gavage), and PG + DOX (200 mg/kg, gavage). After treatment, serum levels of testosterone, interleukin-1β (IL-1β), glutathione (GSH), luteinizing hormone (LH), superoxide dismutase (SOD), lactate dehydrogenase (LDH), catalase (CAT), follicle stimulating hormone (FSH), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA) were measured. Then, gene expression, histopathological, and immunohistochemical analyses were performed on testicular tissues. Compared to DOX, treatment with PG + DOX showed a significant improvement in serum levels of FSH, testosterone, LH, TNF-α, IL-1β, MDA, SOD, LDH, GSH, and CAT. It was also observed that PG + DOX decreased nuclear factor-κB and cyclooxygenase-2 expression levels, increased androgen receptor expression, restored testicular histopathological structure, and significantly improved spermatogenesis. The results of the present study showed that PG may have an ameliorative effect against DOX-induced male reproductive toxicity, as DOX causes male reproductive toxicity. It can be concluded that PG is one of the effects that protect against DOX-induced testicular toxicity in rats by reducing lipid peroxidation and activating the antioxidant system. In light of this information, PG may be a useful agent to prevent the testicular toxicity observed in men receiving DOX treatment.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inherited Genetic Variation in Parkinson's Disease: Convergence on Impaired Autophagosome-Lysosome Fusion Through the Altered Expression of mRNA Isoforms.","authors":"Sreemol Gokuladhas, Catriona Miller, Antony A Cooper, Justin M O'Sullivan","doi":"10.1007/s12035-025-05101-2","DOIUrl":"https://doi.org/10.1007/s12035-025-05101-2","url":null,"abstract":"<p><p>Parkinson's disease (PD) pathogenesis involves complex interactions between genetic factors. We employed two-sample Mendelian randomization (MR) integrating tissue-specific gene regulatory networks to identify causal genes and regulatory elements modulating PD risk. Two-sample MR analysis identified 79 putative causal genes for PD. A subset of the 79 causal genes was enriched within chr17q21.31 and chr16p11.2 cytobands that have been previously linked to neurodevelopmental disorders. Functional enrichment analysis of the 79 genes revealed autophagosome-lysosome fusion as a key process. Ten genes (ELOVL7, HSD3B7, PLEKHM1, PRSS53, SNCA, STX1B, STX4, ZSWIM7, LINC02210, and RP11-1072 A3.3) showed causal associations with tissue-specific expression patterns driving risk or protection for PD. Further investigation into their tissue-specific isoform expression profile revealed isoform-specific contributions to disease risk (or protection). These findings highlight the critical role of isoform-specific expression of causal genes in modulating PD risk, particularly relating to autophagosome-lysosome fusion. While our findings provide new insights into PD susceptibility, we acknowledge that the observed isoform-specific changes may, in part, reflect sample selection bias. Therefore, further experimental verification is needed to confirm the importance of incorporating tissue-specific gene isoform profiles in understanding PD causal mechanisms.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effects of Co-administration of Lactobacillus casei and Bifidobacterium breve vs. Monotherapy on Hippocampal Neurodegeneration in a D-Galactose-Induced Aging Model.","authors":"Olia Hamzeh, Mehrdad Halaji, Maryam Ghasemi-Kasman, Hadi Parsian, Sahar Rostami-Mansoor","doi":"10.1007/s12035-025-05093-z","DOIUrl":"https://doi.org/10.1007/s12035-025-05093-z","url":null,"abstract":"<p><p>It has been shown that gut dysbiosis, a hallmark of aging, participates in age-related neurodegenerative conditions. Consumption of probiotics has favorable effects not only on gut hemostasis but also on the brain via the microbiota-gut-brain axis. Ongoing research aims to identify the most suitable probiotic or combination of probiotics tailored to each specific condition. Hence, the present study tested the effects of combination therapy of Lactobacillus casei (L. casei) and Bifidobacterium breve (B. breve) on the memory and some potential molecular mechanisms of a mouse aging model. Male Balb/C mice were subcutaneously injected with D-galactose to induce aging and orally supplemented with L. casei and B. breve for 8 weeks. The results showed that treatment with L. casei, B. breve, or their co-administration during the aging process improves the impairment of alternation and locomotion behavior in a Y-maze test. Gene expression analysis revealed that consumption of L. casei and B. breve upregulates α-KL, Sirt1, HO-1, and Nrf2 and suppresses IL-1β and IL-18 gene expression in the right hippocampus. Probiotics treatment also reduced the oxidative stress biomarker malondialdehyde (MDA), increased superoxide dismutase (SOD), and mitigated histopathological changes and neurodegeneration in the left hippocampus. Moreover, the level of fluorescent intensity of BDNF was higher in probiotics-receiving groups. Considerably, our study reveals that L. casei shows better performance compared to B. breve, and the combination therapy appears to exhibit a synergistic effect. Together, these findings suggest that a combination of L. casei and B. breve may have better therapeutic potential than monotherapy for controlling oxidative stress and neurodegeneration in aging.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding the Potential Impact of Plasma hsa-miR-24-3p and hsa-miR-181 d-3p Expression, Plasma IFN-γ Levels, and IFNG rs2069727 T/C Genetic Variant on Multiple Sclerosis Risk and Glatiramer Acetate Treatment.","authors":"Mekselina Kalmaz, Semra Mungan, Birsen Can Demirdöğen","doi":"10.1007/s12035-025-05027-9","DOIUrl":"https://doi.org/10.1007/s12035-025-05027-9","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune neurodegenerative disorder, with relapsing-remitting MS (RRMS) being the most common subtype. Interferon-γ (IFN-γ) plays a dual role in MS pathogenesis. MicroRNAs (miRNAs) have emerged as potential diagnostic biomarkers. This study examined the effect of relative expression of hsa-miR-24-3p and hsa-miR-181d-3p, plasma IFN-γ levels, and the IFNG rs2069727 T/C variant on MS risk, evaluating their interrelationships and diagnostic potential. This case-control study comprised two overlapping groups-a genetic polymorphism group (330 RRMS, 330 healthy controls (HCs)) and a miRNA group (25 glatiramer acetate (GA)-treated RRMS patients, 25 treatment-naïve RRMS patients, and 25 HCs)- collected at the Ankara Bilkent City Hospital Neurology Polyclinic. The IFNG rs2069727 T/C variant did not display a statistically significant disparity between RRMS patients and HCs. Significantly elevated hsa-miR-24-3p and hsa-miR-181d-3p relative expression levels were observed in GA-treated and treatment-naïve RRMS patients compared to HCs. Conversely, age-adjusted plasma IFN-γ concentrations were markedly lower in GA-treated and treatment-naïve RRMS patients versus HCs. Individuals with low plasma IFN-γ levels (≤ 1.311 pg/mL) demonstrated significantly elevated hsa-miR-24-3p relative expression compared to the high IFN-γ group (> 1.311 pg/mL). Conversely, subjects with low hsa-miR-181d-3p levels (≤ 2.90) exhibited significantly higher plasma IFN-γ concentrations relative to those with high hsa-miR-181d-3p levels (> 2.90). In the GA-treated group, EDSS negatively correlated with age-adjusted plasma IFN-γ. This study identified age-adjusted plasma IFN-γ, hsa-miR-24-3p, and hsa-miR-181d-3p expression as potential blood-based biomarkers for RRMS diagnosis and analyzed them alongside disability scores. The miRNAs in this study can be further evaluated as prospective therapeutic targets.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT4 Protects Müller Glial Cells Against Apoptosis by Mediating Mitochondrial Dynamics and Oxidative Stress.","authors":"Hongdou Luo, Ming Jin, Haijian Hu, Qian Ying, Piaopiao Hu, Weiwei Sheng, Yi Huang, Ke Xu, Chuming Lu, Xu Zhang","doi":"10.1007/s12035-024-04349-4","DOIUrl":"10.1007/s12035-024-04349-4","url":null,"abstract":"<p><p>SIRT4 is a member of the sirtuin family, which is related to mitochondrial function and possesses antioxidant and regulatory redox effects. Currently, the roles of SIRT4 in retinal Müller glial cells, oxidative stress, and mitochondrial function are still unclear. We confirmed, by immunofluorescence staining, that SIRT4 is located mainly in the mitochondria of retinal Müller glial cells. Using flow cytometry and Western blotting, we analyzed cell apoptosis, intracellular reactive oxygen species (ROS) levels, apoptotic and proapoptotic proteins, mitochondrial dynamics-related proteins, and mitochondrial morphology and number after the overexpression and downregulation of SIRT4 in rMC-1 cells. Neither the upregulation nor the downregulation of SIRT4 alone affected apoptosis. SIRT4 overexpression reduced intracellular ROS, reduced the BAX/BCL2 protein ratio, and increased the L-OPA/S-OPA1 ratio and the levels of the mitochondrial fusion protein MFN2 and the mitochondrial cleavage protein FIS1, increasing mitochondrial fusion. SIRT4 downregulation had the opposite effect. Mitochondria tend to divide after serum starvation for 24 h, and SIRT4 downregulation increases mitochondrial fragmentation and oxidative stress, leading to aggravated cell damage. The mitochondrial division inhibitor Mdivi-1 reduced oxidative stress levels and thus reduced cell damage caused by serum starvation. The overexpression of SIRT4 in rMC-1 cells reduced mitochondrial fragmentation caused by serum starvation, leading to mitochondrial fusion and reduced expression of cleaved caspase-3, thus alleviating the cellular damage caused by oxidative stress. Thus, we speculate that SIRT4 may protect retinal Müller glial cells against apoptosis by mediating mitochondrial dynamics and oxidative stress.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6683-6702"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual Analysis of Research Hotspots and Trends on Mitochondria-Associated Membranes in the Past 20 Years-Focused on Neurodegenerative Diseases.","authors":"Yihang Du, Chenglin Duan, Xueping Zhu, Meng Lyu, Jiafan Chen, Yi Wei, Yuanhui Hu","doi":"10.1007/s12035-025-04722-x","DOIUrl":"10.1007/s12035-025-04722-x","url":null,"abstract":"<p><p>The interaction between mitochondria and the endoplasmic reticulum is mediated by mitochondria-associated endoplasmic reticulum membranes (MAMs), which play a crucial role in regulating intracellular signal transduction and molecular interactions. This study employs bibliometric analysis to examine the research progress on MAMS and identify research hotspots and trends. A total of 1406 publications on MAMs were collected from the Web of Science Core Collection. Software such as CiteSpace, VOSviewer, and Scimago Graphica were utilized in the bibliometric analysis process. This study conducted a bibliometric analysis of over 20 years of MAM research, identifying the countries, institutions, authors, journals, and publications involved in the field. The number of publications on MAMs has been increasing annually since 2010, exhibiting a steady upward trend. The main contributors to this field are the USA, China, and Italy, with the journal Frontiers in Cell and Developmental Biology publishing the most publications. Common keywords include \"endoplasmic reticulum stress,\" \"Ca2 + ,\" \"mitofusin2,\" \"oxidative stress,\" \"apoptosis,\" \"autophagy,\" and \"Alzheimer's disease.\" We found that the role of MAMs in neurodegenerative diseases has aroused great interest among researchers. The associations between calcium homeostasis, autophagy, mitochondrial dysfunction, and cell death with MAMs are also considered research hotspots and show broad research prospects. In addition, changes in MAM-resident proteins, including the mitochondria-ER tethering complex, Mfn2, and Sig-1R, have been highlighted as prominent research directions. The findings provide a comprehensive overview of research on MAMs and valuable insights for researchers, which is helpful for exploring future directions and trends in this field.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7144-7159"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silica Nanoparticles Induce SH-SY5Y Cells Death Via PARP and Caspase Signaling Pathways.","authors":"Kai Ma, Tiantian Tian, Xinyue Li, Huan Pang, Xiaofan Ning, Meng Li, Jiali Li, Zhixuan Luo, Tianxiang Liu, Mengyue Liu, Mingqian Wang, Chao Zhao, Xiuling Song, Haiying Du, Minghua Jin","doi":"10.1007/s12035-025-04724-9","DOIUrl":"10.1007/s12035-025-04724-9","url":null,"abstract":"<p><p>A growing stream of research indicates that exposure to Silica nanoparticles (SiNPs) can cause nervous system damage, leading to the occurrence of neurodegenerative diseases such as Alzheimer's disease. However, the specific mechanism by which SiNPs cause neuroblast injury remains unclear and requires further research. This study established an in vitro experimental model of SH-SY5Y cells exposed to SiNPs and observed cell growth through an inverted fluorescence microscope. Cell viability was measured using an MTT assay. The intracellular ROS and Ca²⁺ levels were detected by flow cytometry. Cell apoptosis was observed using both Hoechst33342 staining and TUNEL staining. The activities of SOD and ATPase and the content of ATP in the cells were tested by biochemical methods. The genes including parp-1, aif, par, ucp2, vdac and prdx3 were explored using quantitative real-time PCR. The expressions of PARP, AIF, PAR, Caspase-3, Caspase-9 and Cyt C proteins were evaluated by Western Blot. The immunofluorescence technique was used to observe the distribution of Parthanatos-related proteins induced by SiNPs. The results showed that SiNPs reduced cell survival rate, induced excessive ROS and Ca²⁺ overload, decreased SOD activity, ATPase activity, intracellular and mitochondrial ATP content, increased the expression of mitochondrial function and PARP pathway related genes, as well as PARP and Caspase pathway protein expression, ultimately inducing cell apoptosis. As a further test of the roles of PARP and Caspase pathways in SiNPs induced SH-SY5Y cells death, we selected the PARP inhibitor Olaparib and Caspase inhibitor Z-VAD, and the above effects were significantly improved after treatment with the inhibitors. Conclusively, this study confirmed that SiNPs can generate excessive ROS production in SH-SY5Y cells, alter mitochondrial function, and induce cell death through Parthanatos and caspase dependent apoptotic pathways, which can coexist and interact with each other.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"7506-7524"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol Inhibits VDAC1-Mediated Mitochondrial Dysfunction to Mitigate Pathological Progression in Parkinson's Disease Model.","authors":"Shenglan Feng, Jianjun Gui, Bingqing Qin, Junjie Ye, Qiang Zhao, Ai Guo, Ming Sang, Xiaodong Sun","doi":"10.1007/s12035-024-04234-0","DOIUrl":"10.1007/s12035-024-04234-0","url":null,"abstract":"<p><p>An increase in α-synuclein (α-syn) levels and mutations in proteins associated with mitochondria contribute to the development of familial Parkinson's disease (PD); however, the involvement of α-syn and mitochondria in idiopathic PD remains incompletely understood. The voltage-dependent anion channel I (VDAC1) protein, which serves as a crucial regulator of mitochondrial function and a gatekeeper, plays a pivotal role in governing cellular destiny through the control of ion and respiratory metabolite flux. The ability of resveratrol (RES), which is a potent phytoalexin with antioxidant and anti-inflammatory properties, to regulate VDAC1 in PD is unknown. The objective of this study was to evaluate the role of VDAC1 in the pathological process of PD and to explore the mechanism by which resveratrol protects dopaminergic neurons by regulating VDAC1 to maintain the mitochondrial permeability transition pore (mPTP) and calcium ion balance. The effects of RES on the motor and cognitive abilities of A53T mice were evaluated by using small animal behavioral tests. Various techniques, including immunofluorescence staining, transmission electron microscopy, enzyme-linked immunoadsorption, quantitative polymerase chain reaction (PCR), and Western blotting, among others, were employed to assess the therapeutic impact of RES on neuropathy associated with PD and its potential in regulating mitochondrial VDAC1. The findings showed that RES significantly improved motor and cognitive dysfunction and restored mitochondrial function, thus reducing oxidative stress levels in A53T mice. A significant positive correlation was observed between the protein expression level of VDAC1 and mitochondrial α-syn expression, as well as disease progression, whereas no such correlation was found in VDAC2 and VDAC3. Administration of RES resulted in a significant decrease in the protein expression of VDAC1 and in the protein expression of α-syn both in vivo and in vitro. In addition, we found that RES prevents excessive opening of the mPTP in dopaminergic neurons. This may prevent the abnormal aggregation of α-syn in mitochondria and the release of mitochondrial apoptosis signals. Furthermore, the activation of VDAC1 reversed the resveratrol-induced decrease in the accumulation of α-syn in the mitochondria. These findings highlight the potential of VDAC1 as a therapeutic target for PD and identify the mechanism by which resveratrol alleviates PD-related pathology by modulating mitochondrial VDAC1.</p>","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"6636-6654"},"PeriodicalIF":4.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}