Molecular Neurobiology最新文献_第7页

Identification of Autophagy-Related Genes in Patients with Acute Spinal Cord Injury and Analysis of Potential Therapeutic Targets. 鉴定急性脊髓损伤患者的自噬相关基因并分析潜在治疗靶点

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-16 DOI: 10.1007/s12035-024-04431-x

Xiaochen Su, Shenglong Wang, Ye Tian, Menghao Teng, Jiachen Wang, Yulong Zhang, Wenchen Ji, Yingang Zhang

{"title":"Identification of Autophagy-Related Genes in Patients with Acute Spinal Cord Injury and Analysis of Potential Therapeutic Targets.","authors":"Xiaochen Su, Shenglong Wang, Ye Tian, Menghao Teng, Jiachen Wang, Yulong Zhang, Wenchen Ji, Yingang Zhang","doi":"10.1007/s12035-024-04431-x","DOIUrl":"10.1007/s12035-024-04431-x","url":null,"abstract":"Autophagy has been implicated in the pathogenesis and progression of spinal cord injury (SCI); however, its specific mechanisms remain unclear. This study is aimed at identifying potential molecular biomarkers related to autophagy in SCI through bioinformatics analysis and exploring potential therapeutic targets. The mRNA expression profile dataset GSE151371 was obtained from the GEO database, and R software was used to screen for differentially expressed autophagy-related genes (DE-ARGs) in SCI. A total of 39 DE-ARGs were detected in this study. Enrichment analysis, protein-protein interaction (PPI) network, TF-mRNA-miRNA regulatory network analysis, and the DSigDB database were used to investigate the regulatory mechanisms between DE-ARGs and identify potential drugs for SCI. Enrichment analysis revealed associations with autophagy, apoptosis, and cell death. PPI analysis identified the highest-scoring module and selected 10 hub genes to construct the TF-mRNA-miRNA network, revealing regulatory mechanisms. Analysis of the DSigDB database indicated that 1,9-Pyrazoloanthrone may be a potential therapeutic drug. Machine learning algorithms identified 3 key genes as candidate biomarkers. Additionally, immune cell infiltration results revealed significant correlations between PINK1, NLRC4, VAMP3, and immune cell accumulation. Molecular docking simulations revealed that imatinib can exert relatively strong regulatory effects on the three key proteins. Finally, in vivo experimental data revealed that the overall biological process of autophagy was disrupted. In summary, this study successfully identified 39 DE-ARGs and discovered several promising biomarkers, significantly contributing to our understanding of the underlying mechanisms of autophagy in SCI. These findings offer valuable insights for the development of novel therapeutic strategies.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2674-2694"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988348","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}

引用次数: 0

The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders. 线粒体丙酮酸载体在神经系统疾病中的作用。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-23 DOI: 10.1007/s12035-024-04435-7

Yue Liu, Xiying Yu, Wei Jiang

{"title":"The Role of Mitochondrial Pyruvate Carrier in Neurological Disorders.","authors":"Yue Liu, Xiying Yu, Wei Jiang","doi":"10.1007/s12035-024-04435-7","DOIUrl":"10.1007/s12035-024-04435-7","url":null,"abstract":"The mitochondrial pyruvate carrier (MPC) is a specific protein complex located in the inner mitochondrial membrane. Comprising a heterodimer of two homodimeric membrane proteins, mitochondrial pyruvate carrier 1 and mitochondrial pyruvate carrier 2, MPC connects cytoplasmic metabolism to mitochondrial metabolism by transferring pyruvate from the cytoplasm to the mitochondria. The nervous system requires substantial energy to maintain its function, and the mitochondrial energy supply is closely linked to neurological function. Mitochondrial dysfunction can induce or exacerbate intracerebral pathologies. MPC influences mitochondrial function due to its specific role as a pyruvate transporter. However, recent studies on MPC and mitochondrial dysfunction in neurological disorders have yielded controversial results, and the underlying mechanisms remain unclear. In this brief review, we provide an overview of the structure and function of MPC. We further discuss the potential mechanisms and feasibility of targeting MPC in treating Parkinson's disease, Alzheimer's disease, and cerebral ischemia/hypoxia injury. This review aims to offer insights into MPC as a target for clinical treatment.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2846-2856"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036409","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}

引用次数: 0

Investigation of Spinocerebellar Ataxia (SCA) Disease in Iranian Patients and Accurate Trinucleotide Repeat Detection in the SCA3 by TP-PCR Method. 伊朗脊髓小脑共济失调症（SCA）患者调查及 TP-PCR 法准确检测 SCA3 中的三核苷酸重复序列

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-19 DOI: 10.1007/s12035-024-04434-8

Shafagh Sharafi, Zahra Rezvani

{"title":"Investigation of Spinocerebellar Ataxia (SCA) Disease in Iranian Patients and Accurate Trinucleotide Repeat Detection in the SCA3 by TP-PCR Method.","authors":"Shafagh Sharafi, Zahra Rezvani","doi":"10.1007/s12035-024-04434-8","DOIUrl":"10.1007/s12035-024-04434-8","url":null,"abstract":"SCA (spinocerebellar ataxia) which is autosomal dominantly transferred is a subset of inherited cerebellar ataxia. These progressive neurological diseases have clinical features of ataxia and are derived from the destruction of the cerebellum. These diseases can also affect other areas, including the brainstem. Frequent proliferation of CAG nucleotides can encode polyglutamine and, as a result, produce the toxic polyglutamine (poly Q) protein that leads to many types of SCAs. They are categorized based on specific genetic mutations. The main symptoms of SCA, gait ataxia and incoordination, nystagmus, vision problems, and dysarthria, can be mentioned. In this study, 31 Iranians who were suspected of SCA disease were clinically diagnosed from November 2019 to September 2021. For these 31 patients suspected of spinocerebellar ataxia, PCR was performed, and the analysis was based on vertical electrophoresis. For SCA3 patients, the TP-PCR technique was carried out and evaluated by capillary electrophoresis. For all 31 patients, PCR function was successful according to the results attained by conventional PCR. The number of three nucleotide replications was within the normal range for 22 people, and nine patients were reported. Studies showed that three people suspected of SCA were infected with SCA3 according to the TP-PCR technique, and this was while seven people were diagnosed with SCA3 using the PCR method. As the purpose of this test is to provide a more accurate diagnostic method and prenatal diagnosis of this disease, the TP-PCR method proved to be more suitable when applied for the diagnosis of abnormal trinucleotides CAG in spinocerebellar ataxia type 3.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2756-2763"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142000338","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}

引用次数: 0

Single-Cell Cortical Transcriptomics Reveals Common and Distinct Changes in Cell-Cell Communication in Alzheimer's and Parkinson's Disease. 单细胞皮层转录组学揭示了阿尔茨海默氏症和帕金森氏症中细胞间通讯的共同和不同变化

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-08-15 DOI: 10.1007/s12035-024-04419-7

Sophie Le Bars, Enrico Glaab

{"title":"Single-Cell Cortical Transcriptomics Reveals Common and Distinct Changes in Cell-Cell Communication in Alzheimer's and Parkinson's Disease.","authors":"Sophie Le Bars, Enrico Glaab","doi":"10.1007/s12035-024-04419-7","DOIUrl":"10.1007/s12035-024-04419-7","url":null,"abstract":"Alzheimer's disease (AD) and Parkinson's disease (PD) cause significant neuronal loss and severely impair daily living. Despite different clinical manifestations, these disorders share common pathological molecular hallmarks, including mitochondrial dysfunction and synaptic degeneration. A detailed comparison of molecular changes at single-cell resolution in the cortex, as one of the main brain regions affected in both disorders, may reveal common susceptibility factors and disease mechanisms. We performed single-cell transcriptomic analyses of post-mortem cortical tissue from AD and PD subjects and controls to identify common and distinct disease-associated changes in individual genes, cellular pathways, molecular networks, and cell-cell communication events, and to investigate common mechanisms. The results revealed significant disease-specific, shared, and opposing gene expression changes, including cell type-specific signatures for both diseases. Hypoxia signaling and lipid metabolism emerged as significantly modulated cellular processes in both AD and PD, with contrasting expression alterations between the two diseases. Furthermore, both pathway and cell-cell communication analyses highlighted shared significant alterations involving the JAK-STAT signaling pathway, which has been implicated in the inflammatory response in several neurodegenerative disorders. Overall, the analyses revealed common and distinct alterations in gene signatures, pathway activities, and gene regulatory subnetworks in AD and PD. The results provide insights into coordinated changes in pathway activity and cell-cell communication that may guide future diagnostics and therapeutics.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"2655-2673"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pharmacologically Targeting Ferroptosis and Cuproptosis in Neuroblastoma. 以神经母细胞瘤中的铁突变和铜突变为药物靶标

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-27 DOI: 10.1007/s12035-024-04501-0

Ying Liu, Joshua S Fleishman, Hongquan Wang, Liang Huo

{"title":"Pharmacologically Targeting Ferroptosis and Cuproptosis in Neuroblastoma.","authors":"Ying Liu, Joshua S Fleishman, Hongquan Wang, Liang Huo","doi":"10.1007/s12035-024-04501-0","DOIUrl":"10.1007/s12035-024-04501-0","url":null,"abstract":"Neuroblastoma is a deadly pediatric cancer that originates from the neural crest and frequently develops in the abdomen or adrenal gland. Although multiple approaches, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, are recommended for treating neuroblastoma, the tumor will eventually develop resistance, leading to treatment failure and cancer relapse. Therefore, a firm understanding of the molecular mechanisms underlying therapeutic resistance is vital for the development of new effective therapies. Recent research suggests that cancer-specific modifications to multiple subtypes of nonapoptotic regulated cell death (RCD), such as ferroptosis and cuproptosis, contribute to therapeutic resistance in neuroblastoma. Targeting these specific types of RCD may be viable novel targets for future drug discovery in the treatment of neuroblastoma. In this review, we summarize the core mechanisms by which the inability to properly execute ferroptosis and cuproptosis can enhance the pathogenesis of neuroblastoma. Therefore, we focus on emerging therapeutic compounds that can induce ferroptosis or cuproptosis, delineating their beneficial pharmacodynamic effects in neuroblastoma treatment. Cumulatively, we suggest that the pharmacological stimulation of ferroptosis and ferroptosis may be a novel and therapeutically viable strategy to target neuroblastoma.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3863-3876"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution. 密码子使用偏差：影响 VGLUT 发育表达和蛋白质进化的潜在因素

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-21 DOI: 10.1007/s12035-024-04426-8

Yiran Zhao, Yu Zhang, Jiaxing Feng, Zixian He, Ting Li

{"title":"Codon Usage Bias: A Potential Factor Affecting VGLUT Developmental Expression and Protein Evolution.","authors":"Yiran Zhao, Yu Zhang, Jiaxing Feng, Zixian He, Ting Li","doi":"10.1007/s12035-024-04426-8","DOIUrl":"10.1007/s12035-024-04426-8","url":null,"abstract":"More and more attention has been paid to the role of synonymous substitution in evolution, in which codon usage preference can affect gene expression distribution and protein structure and function. Vesicular glutamate transporter (VGLUT) consists of three isoforms, among which VGLUT3 is significantly different from other VGLUTs in functional importance, expression level, and distribution range, whose reason is still unclear. This study sought to analyze the role of codon preference in VGLUT differentiation. To conduct an evolutionary analysis of the three VGLUTs, this paper uses bioinformatics research methods to analyze the coding sequences of the three VGLUTs in different species and compare the codon usage patterns. Furthermore, the differences among the three VGLUTs were analyzed by combining functional importance, expression level, distribution range, gene structure, protein relationship network, expression at specific developmental stages, and phylogenetic tree, and the influence of codon usage pattern was explored. The results showed that the VGLUT with greater codon preference had less functional importance, lower expression levels, more peripheral distribution away from the CNS, smaller exon density of gene, less conserved and farther away from the CDS region miRNA regulatory sites, simpler and less tight protein interaction networks, delayed developmental expression, and more distant evolutionary relationships. Codon usage preference is a potential factor affecting VGLUT developmental expression and protein evolution.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3508-3522"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291486","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}

引用次数: 0

Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-MyD88 Pathway in Mice. 1型糖尿病相关肠道微生物群的变化通过丁酸-MyD88途径影响小鼠的微胶质细胞极化，从而加重脑缺血损伤。

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-03-01 Epub Date: 2024-09-26 DOI: 10.1007/s12035-024-04514-9

Xianzhang Zeng, Can Ma, Wenchao Fu, Yongmei Xu, Rui Wang, Dan Liu, Lijuan Zhang, Narisu Hu, Dongmei Li, Wenzhi Li

{"title":"Changes in Type 1 Diabetes-Associated Gut Microbiota Aggravate Brain Ischemia Injury by Affecting Microglial Polarization Via the Butyrate-MyD88 Pathway in Mice.","authors":"Xianzhang Zeng, Can Ma, Wenchao Fu, Yongmei Xu, Rui Wang, Dan Liu, Lijuan Zhang, Narisu Hu, Dongmei Li, Wenzhi Li","doi":"10.1007/s12035-024-04514-9","DOIUrl":"10.1007/s12035-024-04514-9","url":null,"abstract":"People with type 1 diabetes (T1D) have a significantly elevated risk of stroke, but the mechanism through which T1D worsens ischemic stroke remains unclear. This study was aimed at investigating the roles of T1D-associated changes in the gut microbiota in aggravating ischemic stroke and the underlying mechanism. Fecal 16SrRNA sequencing indicated that T1D mice and mice with transplantation of T1D mouse gut microbiota had lower relative abundance of butyric acid producers, f_Erysipelotrichaceae and g_Allobaculum, and lower content of butyric acid in feces. After middle cerebral artery occlusion (MCAO), these mice had poorer neurological outcomes and more severe inflammation, but higher expression of myeloid differentiation factor 88 (MyD88) in the ischemic penumbra; moreover, the microglia were inclined to polarize toward the pro-inflammatory type. Administration of butyrate to T1D mice in the drinking water alleviated the neurological damage after MCAO. Butyrate influenced the response and polarization of BV2 and decreased the production of inflammatory cytokines via MyD88 after oxygen-glucose deprivation/reoxygenation. Knocking down MyD88 in the brain alleviated neurological outcomes and decreased the concentrations of inflammatory cytokines in the brain after stroke in mice with transplantation of T1D mouse gut microbiota. Poor neurological outcomes and aggravated inflammatory responses of T1D mice after ischemic stroke may be partly due to differences in microglial polarization mediated by the gut microbiota-butyrate-MyD88 pathway. These findings provide new ideas and potential intervention targets for alleviating neurological damage after ischemic stroke in T1D.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":"3764-3780"},"PeriodicalIF":4.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350315","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}

引用次数: 0

Critical Role of Rho Guanine Nucleotide Exchange Factor 4 in Brain Function.

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-02-08 DOI: 10.1007/s12035-025-04734-7

Hee Jeong Kim, Kina Lee, Kiseo Yoo, Jeong Eun Kim, Heeju Kim, Chae-Seok Lim, Young Seok Park, Hyong Kyu Kim

{"title":"Critical Role of Rho Guanine Nucleotide Exchange Factor 4 in Brain Function.","authors":"Hee Jeong Kim, Kina Lee, Kiseo Yoo, Jeong Eun Kim, Heeju Kim, Chae-Seok Lim, Young Seok Park, Hyong Kyu Kim","doi":"10.1007/s12035-025-04734-7","DOIUrl":"https://doi.org/10.1007/s12035-025-04734-7","url":null,"abstract":"Although Rho guanine nucleotide exchange factor 4 (Arhgef4) is highly expressed in the brain, its function remains poorly understood. Our previous study showed that Arhgef4 negatively regulates excitatory postsynaptic regional activity. This study investigated the effects of Arhgef4 deletion in postnatal forebrain-specific knockout mice on brain function, synaptic proteins, and behaviors. We generated a knockout mouse with Arhgef4 deleted from the forebrain and analyzed gene expression and protein levels by RT-PCR and western blot. Synaptic function was assessed through electrophysiological recordings, and behavioral tests evaluated memory and anxiety. In these conditional knockout (cKO) mice, we observed a significant decrease in the expression of a 75-kDa brain-enriched isoform of Arhgef4 in the forebrain. In KO mice, pre- and post-synaptic protein levels were unchanged. However, in cultured hippocampal neurons from KO mice, the levels of postsynaptic density protein 95 (PSD-95) in the postsynaptic regions were significantly increased from the pre-mature stage to the fully mature stage during neuronal development. In contrast, the number of dendritic protrusions decreased during the early mature stage of the cultured neurons. Electrophysiological recordings of hippocampal neurons from KO mice showed a significant increase in miniature excitatory postsynaptic currents (mEPSC) frequency. Furthermore, Arhgef4 KO mice exhibited enhanced long-term memory and reduced anxiety-related behaviors. These findings suggest that Arhgef4 plays a role in regulating brain functions such as learning, memory, and anxiety.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370881","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}

引用次数: 0

Pelargonium graveolens Attenuates Rotenone-Induced Parkinson's Disease in a Rat Model: Role of MAO-B Inhibition and In Silico Study.

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-02-08 DOI: 10.1007/s12035-025-04727-6

Rana M Merghany, Salma A El-Sawi, Asmaa F Aboul Naser, Mohamed A Salem, Shahira M Ezzat, Sherifa F A Moustafa, Meselhy R Meselhy

{"title":"Pelargonium graveolens Attenuates Rotenone-Induced Parkinson's Disease in a Rat Model: Role of MAO-B Inhibition and In Silico Study.","authors":"Rana M Merghany, Salma A El-Sawi, Asmaa F Aboul Naser, Mohamed A Salem, Shahira M Ezzat, Sherifa F A Moustafa, Meselhy R Meselhy","doi":"10.1007/s12035-025-04727-6","DOIUrl":"https://doi.org/10.1007/s12035-025-04727-6","url":null,"abstract":"Parkinson's disease (PD), the second most common neurodegenerative condition, is primarily characterized by motor dysfunctions due to dopaminergic neuronal loss in the Substantia Nigra (SN), with oxidative stress playing a significant role in its progression. This study investigates the neuroprotective potential of Pelargonium graveolens (Thunb.) L'Hér leaves in a rotenone-induced PD rat model. The total ethanolic extract and its fractions, obtained via Diaion HP-20 column chromatography, were evaluated for monoamine oxidase-B (MAO-B) inhibition in vitro. The 50% methanol fraction (PG50) demonstrated the highest MAO-B inhibition (IC50 5.26 ± 0.12 µg/ml) compared to the reference drug selegiline (IC50 0.021 ± 0.003 µg/ml). In a rotenone-induced PD rat model, PG50 (100 mg/kg, p.o.) alleviated motor deficits (assessed via the wire hanging test), and restored norepinephrine, dopamine, and serotonin levels. PG50 and L-dopa reduced α-synuclein levels by 367.60% and 377.48%, respectively. Oxidative balance was restored with increased glutathione (23.12%) and decreased malondialdehyde (164.19%) in brain tissues. PG50 significantly reduced serum TNF-α (572.79%) and IL-6 (70.84%) levels, and improved succinate dehydrogenase (14.47%) and lactate dehydrogenase (7.74%) activities in brain tissues. Histopathological alterations in the SN were also ceased. UPLC-MS/MS analysis identified 61 metabolites, including 32 flavonoids, 13 phenolic acids, 7 coumarins, 5 phenolic glycosides, and 4 dicarboxylic acids, with in silico docking showing strong MAO-B binding by methoxylated flavonoids like methoxyluteolin dimethyl ether (docking score: - 8.0625 kcal/mol), surpassing that of safinamide (- 8.2615 kcal/mol). These findings suggest that P. graveolens holds promise as a neuroprotective agent against rotenone-induced PD.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374371","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}

引用次数: 0

Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.

IF 4.6 2区医学

Molecular Neurobiology Pub Date : 2025-02-07 DOI: 10.1007/s12035-025-04725-8

Ritam Mukherjee, Ravi Rana, Sidharth Mehan, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula, Rajaram Samant

{"title":"Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.","authors":"Ritam Mukherjee, Ravi Rana, Sidharth Mehan, Zuber Khan, Ghanshyam Das Gupta, Acharan S Narula, Rajaram Samant","doi":"10.1007/s12035-025-04725-8","DOIUrl":"https://doi.org/10.1007/s12035-025-04725-8","url":null,"abstract":"Neurological illnesses are debilitating diseases that affect brain function and balance. Due to their complicated aetiologies and progressive nature, neurodegenerative and neuropsychiatric illnesses are difficult to treat. These incurable conditions damage brain functions like mobility, cognition, and emotional regulation, but medication, gene therapy, and physical therapy can manage symptoms. Disruptions in cellular signalling pathways, especially those involving oxidative stress response, memory processing, and neurotransmitter modulation, contribute to these illnesses. This review stresses the interplay between key signalling pathways involved in neurological diseases, such as the Nrf2/Keap1/HO-1/SIRT-1 axis and the p75NTR/PI3K/Akt/MAPK cascade. To protect neurons from oxidative damage and death, the Nrf2 transcription factor promotes antioxidant enzyme production. The Keap1 protein releases Nrf2 during oxidative stress for nuclear translocation and gene activation. The review also discusses how neurotrophin signalling through the p75 neurotrophin receptor (p75NTR) determines cell destiny, whether pro-survival or apoptotic. The article highlights emerging treatment approaches targeting these signalling pathways by mapping these connections. Continued research into these molecular pathways may lead to new neurological disease treatments that restore cellular function and neuronal survival. In addition to enhanced delivery technologies, specific modulators and combination therapies should be developed to fine-tune signalling responses. Understanding these crosstalk dynamics is crucial to strengthening neurological illness treatment options and quality of life.","PeriodicalId":18762,"journal":{"name":"Molecular Neurobiology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370882","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}

引用次数: 0