Journal of Molecular Neuroscience最新文献_第7页

The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice ASD 相关基因 CHD8 的缺失会扰乱小鼠的行为模式并抑制海马神经元的形成。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-31 DOI: 10.1007/s12031-024-02283-7

Xiaojie Niu, Feifei Huang, Haizhen Lyu, Jiao Liu, Xinwei Zhang, Jiang Bian, Zhijie Gao, Binyu Liu

{"title":"The Deficiency of the ASD-Related Gene CHD8 Disrupts Behavioral Patterns and Inhibits Hippocampal Neurogenesis in Mice","authors":"Xiaojie Niu, Feifei Huang, Haizhen Lyu, Jiao Liu, Xinwei Zhang, Jiang Bian, Zhijie Gao, Binyu Liu","doi":"10.1007/s12031-024-02283-7","DOIUrl":"10.1007/s12031-024-02283-7","url":null,"abstract":"<div><p>Chromodomain helicase DNA-binding 8 (CHD8) is a gene that poses a high risk for autism spectrum disorder (ASD) and neurological development delay. Nevertheless, the impact of CHD8 haploinsufficiency on both hippocampus neurogenesis and behavior remains uncertain. Here, we performed behavioral assessments on male and female CHD8 heterozygous mice. The study discovered that both male and female CHD8 heterozygous mice displayed an impairment in preference for social novelty. Concurrently, CHD8 heterozygous mice exhibited anxiety-like behavior. However, its cognitive capacity for learning and memory is within the expected range. Furthermore, we discovered a reduction in the number of both immature and mature new neurons in mice with CHD8 heterozygous, resulting in an impeded neurogenesis process in the hippocampus. Taken together, our findings indicate that CHD8 plays a crucial role in the regulation of hippocampal neurogenesis, and further suggest that ASD-like behaviors observed in CHD8 heterozygous mice may be associated with disruptions in hippocampal neurogenesis.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556864","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 Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer’s Disease 非编码 RNA 在阿尔茨海默病线粒体功能障碍中的作用

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-28 DOI: 10.1007/s12031-024-02262-y

Samin Abed, Amir Ebrahimi, Fatemeh Fattahi, Ghazal Kouchakali, Mahmoud Shekari-Khaniani, Sima Mansoori-Derakhshan

{"title":"The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer’s Disease","authors":"Samin Abed, Amir Ebrahimi, Fatemeh Fattahi, Ghazal Kouchakali, Mahmoud Shekari-Khaniani, Sima Mansoori-Derakhshan","doi":"10.1007/s12031-024-02262-y","DOIUrl":"10.1007/s12031-024-02262-y","url":null,"abstract":"<div><p>Although brain amyloid-β (Aβ) peptide buildup is the main cause of Alzheimer’s disease (AD), mitochondrial abnormalities can also contribute to the illness’s development, as either a primary or secondary factor, as programmed cell death and efficient energy generation depend on the proper operation of mitochondria. As a result, non-coding RNAs (ncRNAs) may play a crucial role in ensuring that nuclear genes related to mitochondria and mitochondrial genes function normally. Interestingly, a significant number of recent studies have focused on the impact of ncRNAs on the expression of nucleus and mitochondrial genes. Additionally, researchers have proposed some intriguing therapeutic approaches to treat and reduce the severity of AD by adjusting the levels of these ncRNAs. The goal of this work was to consolidate the existing knowledge in this field of study by systematically investigating ncRNAs, with a particular emphasis on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs). Therefore, the impact and processes by which ncRNAs govern mitochondrial activity in the onset and progression of AD are thoroughly reviewed in this article. Collectively, the effects of ncRNAs on physiological and molecular mechanisms associated with mitochondrial abnormalities that exacerbate AD are thoroughly reviewed in the current research, while also emphasizing the relationship between disturbed mitophagy in AD and ncRNAs.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02262-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142518843","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 and Clinical Characterization of a Cohort of Autosomal Recessive Sensorineural Hearing Loss in Egyptian Patients 一组埃及常染色体隐性感音神经性听力损失患者的分子和临床特征。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-28 DOI: 10.1007/s12031-024-02279-3

Mohammed M. Sayed-Ahmed, Hala T. El-Bassyouni, Hanan H. Afifi, Mona L. Essawi, Mohamed B. Taher, Mohamed I. Gadelhak, Rehab A. Zaytoun, Ahmed A. Abdelmonem, Nagham M. Elbagoury

{"title":"Molecular and Clinical Characterization of a Cohort of Autosomal Recessive Sensorineural Hearing Loss in Egyptian Patients","authors":"Mohammed M. Sayed-Ahmed, Hala T. El-Bassyouni, Hanan H. Afifi, Mona L. Essawi, Mohamed B. Taher, Mohamed I. Gadelhak, Rehab A. Zaytoun, Ahmed A. Abdelmonem, Nagham M. Elbagoury","doi":"10.1007/s12031-024-02279-3","DOIUrl":"10.1007/s12031-024-02279-3","url":null,"abstract":"<div><p>Hearing loss (HL) is one of the most common health problems worldwide. Autosomal recessive non-syndromic sensorineural hearing loss (ARNSHL) represents a large portion of congenital hereditary HL. Our study was conducted on 13 patients from 13 unrelated families. The majority of patients presented with congenital severe to profound bilateral sensorineural HL. All patients were subjected to detailed family history and three-generation pedigree analysis to exclude any environmental cause and to ensure an autosomal recessive mode of inheritance. Molecular analysis was performed using the whole exome sequencing (WES) technique for the recruited patients. Three variants in the <i>MYO7A</i> and <i>OTOF</i> genes were reported for the first time in patients with ARNSHL (one nonsense, one frameshift, and one splice variant). Ten previously reported variants were detected in seven genes (<i>GJB2</i>, <i>MYO15A</i>, <i>BSND</i>, <i>OTOF</i>, <i>CDH23</i>, <i>SLC26A4</i>, and <i>TMIE</i>). They varied between missense, nonsense, frameshift, and splice variants. This study expands the molecular spectrum of two types of autosomal recessive deafness (types 2 and 9).</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02279-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520611","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

Signaling Pathways Concerning Mitochondrial Dysfunction: Implications in Neurodegeneration and Possible Molecular Targets 与线粒体功能障碍有关的信号通路：神经退行性变的影响和可能的分子靶标

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-28 DOI: 10.1007/s12031-024-02269-5

Yati Sharma, Jeetendra Kumar Gupta, M. Arockia Babu, Sumitra Singh, Rakesh K. Sindhu

{"title":"Signaling Pathways Concerning Mitochondrial Dysfunction: Implications in Neurodegeneration and Possible Molecular Targets","authors":"Yati Sharma, Jeetendra Kumar Gupta, M. Arockia Babu, Sumitra Singh, Rakesh K. Sindhu","doi":"10.1007/s12031-024-02269-5","DOIUrl":"10.1007/s12031-024-02269-5","url":null,"abstract":"<div><p>Mitochondrion is an important organelle present in our cells responsible for meeting energy requirements. All higher organisms rely on efficient mitochondrial bioenergetic machinery to sustain life. No other respiratory process can produce as much power as generated by mitochondria in the form of ATPs. This review is written in order to get an insight into the magnificent working of mitochondrion and its implications in cellular homeostasis, bioenergetics, redox, calcium signaling, and cell death. However, if this machinery gets faulty, it may lead to several disease states. Mitochondrial dysfunctioning is of growing concern today as it is seen in the pathogenesis of several diseases which includes neurodegenerative disorders, cardiovascular disorders, diabetes mellitus, skeletal muscle defects, liver diseases, and so on. To cover all these aspects is beyond the scope of this article; hence, our study is restricted to neurodegenerative disorders only. Moreover, faulty functioning of this organelle can be one of the causes of early ageing in individuals. This review emphasizes mutations in the mitochondrial DNA, defects in oxidative phosphorylation, generation of ROS, and apoptosis. Researchers have looked into new approaches that might be able to control mitochondrial failure and show a lot of promise as treatments.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02269-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142518844","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 Novel Pathogenic Mutation in WNK1 Gene Causing HSAN Type II in Three Siblings WNK1 基因中的一种新型致病突变导致三个兄弟姐妹中出现 HSAN II 型。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-23 DOI: 10.1007/s12031-024-02282-8

Maryam Naghinejad, Amir Ebrahimi, Mahmoud Shekari Khaniani, Sima Mansoori Derakhshan

{"title":"A Novel Pathogenic Mutation in WNK1 Gene Causing HSAN Type II in Three Siblings","authors":"Maryam Naghinejad, Amir Ebrahimi, Mahmoud Shekari Khaniani, Sima Mansoori Derakhshan","doi":"10.1007/s12031-024-02282-8","DOIUrl":"10.1007/s12031-024-02282-8","url":null,"abstract":"<div><p>Hereditary sensory and autonomic neuropathy (HSAN) is a rare genetic disorder that primarily affects the peripheral nervous system, leading to a progressive loss of the ability to perceive pain, temperature, and touch. This condition can result in severe complications, including injuries and infections due to the inability to feel pain. HSAN is classified into nine types, with types I and VII exhibiting autosomal dominant inheritance, while the others follow an autosomal recessive pattern. In this study, we examined three affected brothers of Turkish Azeri descent, aged 20, 23, and 25 years. They presented symptoms such as a lack of temperature and pain sensation, frequent wounds and infections, self-harm, and hyperkeratosis. To identify the genetic cause of their condition, whole-exome sequencing (WES) was performed, followed by Sanger sequencing to confirm the findings. The results revealed a homozygous likely pathogenic nonsense mutation, c.2971C > T (p.Arg991Ter), in exon 9 of the <i>WNK1</i> gene. This mutation results in the truncation of three isoforms of the WNK1 protein, which are essential for pain perception. This discovery enhances our understanding of HSAN and highlights the importance of genetic testing for accurate diagnosis and future screening.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492605","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

Effects of Electroacupuncture at Varied Frequencies on Analgesia and Mechanisms in Sciatic Nerve Cuffing-Induced Neuropathic Pain Mice 不同频率的电针对坐骨神经袖带诱发神经性疼痛小鼠的镇痛效果和机制的影响

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-17 DOI: 10.1007/s12031-024-02276-6

Kexin Fang, Wen Cheng, Bin Yu

{"title":"Effects of Electroacupuncture at Varied Frequencies on Analgesia and Mechanisms in Sciatic Nerve Cuffing-Induced Neuropathic Pain Mice","authors":"Kexin Fang, Wen Cheng, Bin Yu","doi":"10.1007/s12031-024-02276-6","DOIUrl":"10.1007/s12031-024-02276-6","url":null,"abstract":"<div><p>Addressing the intricate challenge of chronic neuropathic pain has significant implications for the physical and psychological well-being of patients, given its enduring nature. In contrast to opioids, electroacupuncture (EA) may potentially provide a safer and more efficacious therapeutic alternative. Our objective is to investigate the distinct analgesic effects and potential mechanisms of EA at frequencies of 2 Hz, 100 Hz, and 18 kHz in order to establish more precise frequency selection criteria for clinical interventions. Analgesic efficacy was evaluated through the measurement of mice’s mechanical and thermal pain thresholds. Spinal cord inflammatory cytokines and neuropeptides were quantified via Quantitative Real-time PCR (qRT-PCR), Western blot, and immunofluorescence. Additionally, RNA sequencing (RNA-Seq) was conducted on the spinal cord from mice in the 18 kHz EA group for comprehensive transcriptomic analysis. The analgesic effect of EA on neuropathic pain in mice was frequency-dependent. Stimulation at 18 kHz provided superior and prolonged relief compared to 2 Hz and 100 Hz. Our research suggests that EA at frequencies of 2 Hz, 100 Hz, and 18 kHz significantly reduce the release of inflammatory cytokines. The analgesic effects of 2 Hz and 100 Hz stimulation are due to frequency-dependent regulation of opioid release in the spinal cord. Furthermore, 18 kHz stimulation has been shown to reduce spinal neuronal excitability by modulating the serotonergic pathway and downstream receptors in the spinal cord to alleviate neuropathic pain.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02276-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443342","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 Inhibition of Reactive Oxygen Species Modulator 1 Attenuates Sevoflurane-Induced Neural Injury via Reducing Apoptosis and Oxidative Stress 抑制活性氧调节因子 1 可通过减少细胞凋亡和氧化应激减轻七氟醚诱导的神经损伤

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-16 DOI: 10.1007/s12031-024-02277-5

Lingyan Gu, Xuehu Wang, Zhihao Wu, Jiawei Chen

{"title":"The Inhibition of Reactive Oxygen Species Modulator 1 Attenuates Sevoflurane-Induced Neural Injury via Reducing Apoptosis and Oxidative Stress","authors":"Lingyan Gu, Xuehu Wang, Zhihao Wu, Jiawei Chen","doi":"10.1007/s12031-024-02277-5","DOIUrl":"10.1007/s12031-024-02277-5","url":null,"abstract":"<div><p>Sevoflurane causes neural injury by promoting apoptosis and oxidative stress. Reactive oxygen species modulator 1 (ROMO1) regulates apoptosis and oxidative stress, while its role in sevoflurane-induced neural injury remains unclear. This study intended to investigate the effect of ROMO1 knockdown on viability, apoptosis, and oxidative stress in sevoflurane-treated HT22 cells and its downstream pathway. HT22 cells were untreated (blank control), or treated with 1%, 2%, and 4% sevoflurane, respectively. Moreover, HT22 cells were transfected with siROMO1 small interfering RNA (siROMO1) or negative control siRNA (siNC) and then stimulated with 4% sevoflurane for further assays. Sevoflurane dose-dependently decreased cell viability and increased apoptosis rate versus blank control in HT22 cells. Sevoflurane elevated reactive oxygen species (ROS) fluorescence intensity, malondialdehyde (MDA), and lactate dehydrogenase (LDH) release, while reducing superoxide dismutase (SOD) activity in a dose-dependent manner versus blank control in HT22 cells. It also dose-dependently increased the relative mRNA and protein expressions of ROMO1 versus blank treatment in HT22 cells. Moreover, siROMO1 plus 4% sevoflurane increased cell viability, while decreasing apoptosis rate, ROS fluorescence intensity, MDA, and LDH release versus siNC plus 4% sevoflurane in HT22 cells. siROMO1 plus 4% sevoflurane elevated the phosphorylation of protein kinase B (AKT) versus siNC plus 4% sevoflurane in HT22 cells. ROMO1 inhibition reverses sevoflurane-induced neural injury by reducing apoptosis and oxidative stress in HT22 cells. The results indicate that ROMO1 may be a potential target for the management of sevoflurane-induced neural injury.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443177","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

Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization 探索帕金森病中补体系统相关基因的中枢基因和潜在机制：基于转录组测序和孟德尔随机化。

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-07 DOI: 10.1007/s12031-024-02272-w

Xin Wang, Gaoming Yang, Yali Lai, Yuanyuan Li, Xindong Liu

{"title":"Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization","authors":"Xin Wang, Gaoming Yang, Yali Lai, Yuanyuan Li, Xindong Liu","doi":"10.1007/s12031-024-02272-w","DOIUrl":"10.1007/s12031-024-02272-w","url":null,"abstract":"<div><p>An accurate diagnosis of Parkinson’s disease (PD) remains challenging and the exact cause of the disease is unclean. The aims are to identify hub genes associated with the complement system in PD and to explore their underlying molecular mechanisms. Initially, differentially expressed genes (DEGs) and key module genes related to PD were mined through differential expression analysis and WGCNA. Then, differentially expressed CSRGs (DE-CSRGs) were obtained by intersecting the DEGs, key module genes and CSRGs. Subsequently, MR analysis was executed to identify genes causally associated with PD. Based on genes with significant MR results, the expression level and diagnostic performance verification were achieved to yield hub genes. Functional enrichment and immune infiltration analyses were accomplished to insight into the pathogenesis of PD. qRT-PCR was employed to evaluate the expression levels of hub genes. After MR analysis and related verification, CD93, CTSS, PRKCD and TLR2 were finally identified as hub genes. Enrichment analysis indicated that the main enriched pathways for hub genes. Immune infiltration analysis found that the hub genes showed significant correlation with a variety of immune cells (such as myeloid-derived suppressor cell and macrophage). In the qRT-PCR results, the expression levels of CTSS, PRKCD and TLR2 were consistent with those we obtained from public databases. Hence, we mined four hub genes associated with complement system in PD which provided novel perspectives for the diagnosis and treatment of PD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379823","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

Identification of Pathogenic Missense Mutations of NF1 Using Computational Approaches 利用计算方法鉴定 NF1 的致病性错义突变

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-07 DOI: 10.1007/s12031-024-02271-x

Jie Chen, Ziqiao Li, Yiheng Wu, Xiang Li, Zipei Chen, Pan Chen, Yuhan Ding, Chengpeng Wu, Lidan Hu

{"title":"Identification of Pathogenic Missense Mutations of NF1 Using Computational Approaches","authors":"Jie Chen, Ziqiao Li, Yiheng Wu, Xiang Li, Zipei Chen, Pan Chen, Yuhan Ding, Chengpeng Wu, Lidan Hu","doi":"10.1007/s12031-024-02271-x","DOIUrl":"10.1007/s12031-024-02271-x","url":null,"abstract":"<div><p>Neurofibromatosis type 1 (NF1) is a prevalent autosomal dominant disorder caused by mutations in the NF1 gene, leading to multisystem disorders. Given the critical role of cysteine residues in protein stability and function, we aimed to identify key NF1 mutations affecting cysteine residues that significantly contribute to neurofibromatosis pathology. To identify the most critical mutations in the <i>NF1</i> gene that contribute to the pathology of neurofibromatosis, we employed a sophisticated computational pipeline specifically designed to detect significant mutations affecting the <i>NF1</i> gene. Our approach involved an exhaustive search of databases such as the Human Gene Mutation Database (HGMD), UniProt, and ClinVar for information on missense mutations associated with <i>NF1</i>. Our search yielded a total of 204 unique cysteine missense mutations. We then employed in silico prediction tools, including PredictSNP, iStable, and Align GVGD, to assess the impact of these mutations. Among the mutations, C379R, R1000C, and C1016Y stood out due to their deleterious effects on the biophysical properties of the neurofibromin protein, significantly destabilizing its structure. These mutations were subjected to further phenotyping analysis using SNPeffect 4.0, which predicted disturbances in the protein’s chaperone binding sites and overall structural stability. Furthermore, to directly visualize the impact of these mutations on protein structure, we utilized AlphaFold3 to simulate both the wild-type and mutant NF1 structures, revealing the significant effects of the R1000C mutation on the protein’s conformation. In conclusion, the identification of these mutations can play a pivotal role in advancing the field of precision medicine and aid in the development of effective drugs for associated diseases.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379824","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 Best–Worst Job in the World: When Reality Meets the Brain 世界上最糟糕的工作：当现实与大脑相遇

IF 2.8 4区医学

Journal of Molecular Neuroscience Pub Date : 2024-10-07 DOI: 10.1007/s12031-024-02275-7

Noam Shomron

引用次数: 0