Journal of Molecular Neuroscience最新文献

{"title":"The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme","authors":"Yafei Wang,&nbsp;Ying Yu,&nbsp;Jiahua Yu,&nbsp;Cheng Wang,&nbsp;Yunkun Wang,&nbsp;Runxi Fu,&nbsp;Chenran Zhang","doi":"10.1007/s12031-024-02285-5","DOIUrl":"10.1007/s12031-024-02285-5","url":null,"abstract":"<div><p>Primary brain tumors that were the most severe and aggressive were called glioblastoma multiforme (GBM). Cancers are caused in part by aberrant expression of circular RNA. Often referred to as competitive endogenous RNA (ceRNA), circRNA molecules act as “miRNA sponges” in cells by decreasing the inhibitory impact of miRNA on their target genes and hence raising the expression levels of those genes. circRNA molecules are rich in miRNA binding sites. The discovery of more structurally diverse and GBM-related circRNAs has great promise for the use of GMB prognostic biomarkers and therapeutic targets, as well as for comprehending the molecular regulatory mechanisms of GBM. In this work, we present an overview of the circRNA expression patterns associated with GBM and offer a potential integrated electrochemical strategy for detecting circRNA with extreme sensitivity in the diagnosis of glioblastoma.</p><h3>Graphical Abstract</h3><p>The circular RNA (circRNA) regulates both physiological and pathological processes in glioblastoma multiforme disease. Hence, it could serve as a biomarker as well as a therapeutic target.</p>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995624","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}

{"title":"Diagnostic Value of Serum miR-499a-5p in Chinese Children with Autism Spectrum Disorders","authors":"Jie Ren,&nbsp;Yanle Bai,&nbsp;Jielin Gao,&nbsp;Yafei Hou,&nbsp;Jie Mao,&nbsp;Fengxiao Gao,&nbsp;Jiaqi Wang","doi":"10.1007/s12031-024-02296-2","DOIUrl":"10.1007/s12031-024-02296-2","url":null,"abstract":"<div><p>The purpose of this study was to investigate the expression of miR-499a-5p in children with autism spectrum disorders (ASD) and its value in early diagnosis of ASD. This is a retrospective case–control study that included 40 children with ASD as a case group and 43 healthy children as a control group. Magnetic resonance imaging (MRI) was performed on all subjects, and the children were scored with childhood autism rating scale (CARS) and autism behavior checklist (ABC). The expression of miR-499a-5p in serum was detected by RT-qPCR, and the diagnostic value of miR-499a-5p in ASD was evaluated by ROC curve. Pearson correlation coefficient was used to evaluate the correlation between miR-499a-5p levels and scores. Compared with healthy children, the expression level of serum miR-499a-5p was significantly reduced in children with ASD. ROC curve showed that miR-499a-5p is of high diagnostic value for ASD. The results of MRI suggested that the volume of the amygdala in ASD children was significantly larger than that in healthy children, while the volume of the caudate nucleus was significantly reduced. Correlation results showed that the scores of CARS and ABC in the ASD group were significantly negatively correlated with the levels of miR-499a-5p. In the ASD group, the volume of the amygdala was negatively correlated with the level of miR-499a-5p, while the volume of the caudate nucleus was positively correlated with the level of miR-499a-5p. The decreased expression of miR-499a-5p in the serum of children with ASD was significantly related to the changes in brain volume of children with ASD, and the miRNA showed good diagnostic accuracy in children with ASD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995755","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}

{"title":"Exploring Brain Imaging and Genetic Risk Factors in Different Progression States of Alzheimer’s Disease Through OSnetNMF-Based Methods","authors":"Min Gao,&nbsp;Wei Kong,&nbsp;Kun Liu,&nbsp;Gen Wen,&nbsp;Yaling Yu,&nbsp;Yuemin Zhu,&nbsp;Zhihan Jiang,&nbsp;Kai Wei","doi":"10.1007/s12031-024-02274-8","DOIUrl":"10.1007/s12031-024-02274-8","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment, often preceded by mild cognitive impairment (MCI). Multimodal imaging genetics integrates imaging and genetic data to gain a deeper understanding of disease progression and individual variations. This study focuses on exploring the mechanisms that drive the transition from normal cognition to MCI and ultimately to AD. As an effective joint feature extraction and dimensionality reduction method, non-negative matrix factorization (NMF) and its improved variants, particularly the network-based non-negative matrix factorization (netNMF), have been widely used in multimodal analysis to mine brain imaging and genetic data by considering the interactions between different features. However, many of these methods overlook the importance of the coefficient matrix and do not address issues related to data accuracy and feature redundancy. To address these limitations, we propose an orthogonal sparse network non-negative matrix factorization (OSnetNMF) algorithm, which introduces orthogonal and sparse constraints based on netNMF. By establishing linear relationships between structural magnetic resonance imaging (sMRI) and corresponding gene expression data, OSnetNMF reduces feature redundancy and decreases correlation between data, resulting in more accurate and reliable biomarker extraction. Experiments demonstrate that the OSnetNMF algorithm can accurately identify risk regions of interest (ROIs) and key genes that characterize AD progression, revealing significant trends in ROI pairs such as l4thVen-HIF1A, rBst-MPO, and rBst-PTK2B. Comparative experiments show that the improved algorithm outperforms traditional methods, identifying more disease-related biomarkers and achieving better reconstruction performance.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142994546","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}

{"title":"Deciphering Necroptosis-Associated Molecular Subtypes in Acute Ischemic Stroke Through Bioinformatics and Machine Learning Analysis","authors":"Zongkai Wu,&nbsp;Hongzhen Fan,&nbsp;Lu Qin,&nbsp;Xiaoli Niu,&nbsp;Bao Chu,&nbsp;Kaihua Zhang,&nbsp;Yaran Gao,&nbsp;Hebo Wang","doi":"10.1007/s12031-024-02241-3","DOIUrl":"10.1007/s12031-024-02241-3","url":null,"abstract":"<div><p>Acute ischemic stroke (AIS) is a severe disorder characterized by complex pathophysiological processes, which can lead to disability and death. This study aimed to determine necroptosis-associated genes in acute ischemic stroke (AIS) and to investigate their potential as diagnostic and therapeutic targets for AIS. Expression profiling data were acquired from the Gene Expression Omnibus database, and necroptosis-associated genes were retrieved from GeneCards. The differentially expressed genes (DEGs) and necroptosis-related genes were intersected to obtain the necroptosis-related DEGs (NRDEGs) in AIS. In AIS, a total of 76 genes associated with necroptosis (referred to as NRDEGs) were identified. Enrichment analysis of these genes revealed that they were primarily enriched in pathways known to induce necroptosis. Using weighted gene co-expression network analysis (WGCNA), five co-expression modules consisting of NRDEGs were identified, along with two modules that exhibited a strong correlation with AIS. Protein–protein interaction (PPI) analysis resulted in the identification of 20 hub genes. The Least absolute shrinkage and selection operator (LASSO) regression model demonstrated promising potential for diagnostic prediction. The receiver operating characteristic (ROC) curve validated the diagnostic model and selected nine characteristic genes that exhibited statistically significant differences (<i>p</i> &lt; 0.05). By employing consensus clustering, distinct patterns of necroptosis were identified using these nine signature genes. The results were validated by quantitative PCR (qPCR) in venous blood from patients with AIS and healthy controls and HT22 cells, as well as external datasets. Furthermore, the analyzed ceRNA network included nine lncRNAs, six miRNAs, and three mRNAs. Overall, this study offers novel insights into the molecular mechanisms underlying NRDEGs in AIS. The findings provide valuable evidence and contribute to our understanding of the disease.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12031-024-02241-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912996","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}

{"title":"α7-Nicotinic Acetylcholine Receptor Activation Modulates BV2 Microglial Plasticity via miR-21/TNF-α/NFκB in Oxygen–Glucose Deprivation/Reoxygenation","authors":"Mohammad Yusuf Hasan,&nbsp;Azim Haikal Md Roslan,&nbsp;Norazrina Azmi,&nbsp;Norlinah Mohamed Ibrahim,&nbsp;Alina Arulsamy,&nbsp;Vanessa Lin Lin Lee,&nbsp;Rosfaiizah Siran,&nbsp;Sharmili Vidyadaran,&nbsp;Eng Wee Chua,&nbsp;Mohd Kaisan Mahadi","doi":"10.1007/s12031-024-02300-9","DOIUrl":"10.1007/s12031-024-02300-9","url":null,"abstract":"<div><p>Elevated inflammatory reactions are a significant component in cerebral ischemia–reperfusion injury (CIRI). Activation of α7-Nicotinic Acetylcholine Receptor (α7nAChR) reduces stroke-induced inflammation in rats, but the anti-inflammatory pathway in microglia under CIRI condition remains unclear. This study employed qRT-PCR, protein assays, NanoString analysis, and bioinformatics to examine the effects of PNU282987 treatment (α7nAChR agonist) on BV2 microglial functional differentiation in oxygen–glucose deprivation/reoxygenation (OGDR) condition. OGDR significantly increased the gene expression of pro-inflammatory markers such as TNF-α, IL-6, and IL1β, while α7nAChR agonists reduced these markers. The anti-inflammatory gene marker IL-10 was upregulated by α7nAChR agonist treatment. Downstream pathway marker analysis showed that both gene and protein expression of NFκB was associated with anti-inflammatory effects. Blocking microRNA-21 with antagomir reversed the anti-inflammatory effects. NanoString analysis revealed that microRNA-21 inhibition significantly affected inflammation-related genes, including <i>AL1RAP</i>, <i>TLR9</i>, <i>FLT1</i>, <i>PTGIR</i>, <i>NFκB</i>, <i>TREM2</i>, <i>TNF</i>, <i>SMAD7</i>, <i>FOS</i>, <i>CCL5</i>, <i>IFIT1</i>, <i>CFB</i>, <i>CXCL10</i>, <i>IFI44</i>, <i>DDIT3</i>, <i>IRF7</i>, <i>OASL1</i>, <i>IL1A</i>, <i>IFIT2</i>, <i>C3</i>, <i>CD40</i>, <i>STAT2</i>, <i>IFIT3</i>, <i>IL1RN</i>, <i>OAS1A</i>, <i>CSF1</i>, <i>CCL4</i>, <i>CCL2</i>, <i>CCL3</i>, <i>BCL2L1</i>, and <i>ITGB2</i>. Enrichment analysis of upregulated genes identified Gene Ontology Biological Processes related to cytokine responses and TNF-associated pathways. This study highlights α7nAChR activation as a key regulator of anti-inflammatory responses in BV2 microglia under OGDR conditions, with micro-RNA21 identified as a crucial mediator of receptor-driven neuroprotection via the TNF-α/NF<i>κ</i>B signalling pathway.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880486","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}

{"title":"MicroRNA Expression Profile Is Altered by Short-Term and Chronic Lithium Treatment in a Rat Model of Depression","authors":"Maria Kachel,&nbsp;Antonina Dola,&nbsp;Mikołaj Kubiak,&nbsp;Wiktoria Majewska,&nbsp;Joanna Nowakowska,&nbsp;Wojciech Langwiński,&nbsp;Szymon Hryhorowicz,&nbsp;Aleksandra Szczepankiewicz","doi":"10.1007/s12031-024-02298-0","DOIUrl":"10.1007/s12031-024-02298-0","url":null,"abstract":"<div><p>Depression is a common disease that affects 3.8% of the global population. Despite various antidepressant treatments, one-third of patients do not respond to antidepressants, therefore augmentation with mood stabilizers such as lithium may be required in this group. One of the suggested pathomechanisms of depression is the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and recent reports showed that microRNAs (miRNA) can impact its activity by epigenetic regulation. We aimed to explore the miRNA expression profile in the depression model and its changes upon short-term and chronic lithium treatment in the rat brain (pituitary, hypothalamus, and hippocampus). We used a chronic mild stress rat model of depression and short- and long-term lithium treatment. The behavior was assessed by an open-field test. The miRNA expression profile in the pituitary was estimated by sequencing and validated in the hypothalamus and hippocampus with qPCR. We found several miRNAs in the pituitary that were significantly altered between CMS-exposed and control rats as well as after short- and long-term lithium treatment. MicroRNAs chosen for validation in the hypothalamus and hippocampus (rno-miR-146a-5p, rno-miR-127-3p) showed no significant changes in expression. We performed in silico analysis and estimated potential pathways involved in lithium action for miRNAs differentially expressed in the pituitary at different time points. Specific microRNA subsets showed altered expression in the pituitary in depression model upon short- and long-term lithium treatment. We identified that biological pathways of target genes for these altered miRNAs differ, with the Foxo pathway potentially involved in disease development.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821386","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}

{"title":"Exploring the Role of Chemokine-Related Gene Deregulation and Immune Infiltration in Ischemic Stroke: Insights into CXCL16 and SEMA3E as Potential Biomarkers","authors":"Tingting Yu,&nbsp;Peng Jiang","doi":"10.1007/s12031-024-02295-3","DOIUrl":"10.1007/s12031-024-02295-3","url":null,"abstract":"<div><p>Ischemic stroke is a leading cause of mortality and disability globally. Understanding the role of chemokine-related differently expressed genes (CDGs) in ischemic stroke pathophysiology is essential for advancing diagnostic and therapeutic strategies. We conducted comprehensive analyses using the GSE16561 dataset: chemokine pathway enrichment via GSVA, differential expression of 12 CDGs, Pearson correlation, and functional enrichment analyses (GO and KEGG). Machine learning algorithms were employed to develop diagnostic models, evaluated using ROC curve analysis. A nomogram was constructed and validated with independent datasets (GSE58294). Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were also performed. Chemokine pathway scores were significantly elevated in ischemic stroke, indicating their potential involvement. Logistic regression emerged as the most effective diagnostic model, with CXCL16 and SEMA3E as significant biomarkers. The nomogram exhibited high discriminatory ability (AUC = 0.964), well-calibrated predictions, and clinical utility across datasets. GSEA highlighted key biological pathways associated with CXCL16 and SEMA3E. Immuno-infiltration analysis revealed significant differences in immune cell infiltration between control and ischemic stroke groups, with distinct correlations between CXCL16 and SEMA3E expression and immune cell populations. This study highlights the deregulation of CDGs in ischemic stroke and their implications in critical biological processes. CXCL16 and SEMA3E are identified as key biomarkers with potential diagnostic utility. Insights from gene set enrichment and immuno-infiltration analyses provide mechanistic understanding, suggesting novel therapeutic targets and enhancing clinical decision-making in ischemic stroke management.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811181","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}

{"title":"Melatonin’s Impact on Cytokine Storm and Modulation of Purinergic Receptors for COVID-19 Prognosis: A Mental Health Perspective","authors":"Amanda Gollo Bertollo,&nbsp;Joana Bortolanza Dalazen,&nbsp;Joana Vitória Cassol,&nbsp;Mariélly Braun Hellmann,&nbsp;Tiago Libério Mota,&nbsp;Zuleide Maria Ignácio,&nbsp;Margarete Dulce Bagatini","doi":"10.1007/s12031-024-02292-6","DOIUrl":"10.1007/s12031-024-02292-6","url":null,"abstract":"<div><p>In 2019, coronavirus disease 2019 (COVID-19) started a global health crisis and was associated with high rates of depression and anxiety. Both mental disorders and COVID-19 exhibit similarities in pathophysiology, characterized by immune system overactivation, involvement of the purinergic system, and oxidative stress, besides additional factors and systems likely contributing to the complexities of these conditions. The purinergic system contributes to the disease-influenced immune response, an essential strategy for controlling pathophysiological effects. In this context, the hormone melatonin emerges as a substance that can modulate the purinergic system and contribute positively to the pathophysiology of SARS-CoV-2 infection and associated mental disorders. Melatonin is a hormone that regulates the body’s circadian rhythms, plays an essential role in regulating sleep and mood, and modulates the purinergic system. Recent studies suggest melatonin’s anti-inflammatory and antioxidant properties may benefit COVID-19. This review explores melatonin’s impact on inflammatory cytokine storm in COVID-19 through purinergic system modulation.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778524","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}

{"title":"Valproate Administration to Adult 5xFAD Mice Upregulates Expression of Neprilysin and Improves Olfaction and Memory","authors":"Dmitrii S. Vasilev,&nbsp;Nadezhda M. Dubrovskaya,&nbsp;Natalia L. Tumanova,&nbsp;Aleksandr N. Tursunov,&nbsp;Natalia N. Nalivaeva","doi":"10.1007/s12031-024-02287-3","DOIUrl":"10.1007/s12031-024-02287-3","url":null,"abstract":"<div><p>It is well known that the development of neurodegeneration, and especially Alzheimer’s disease (AD), is often accompanied by impaired olfaction which precedes memory loss. A neuropeptidase neprilysin (NEP)—a principal amyloid-degrading enzyme in the brain—was also shown to be involved in olfactory signalling. Previously we have demonstrated that 5xFAD mice develop olfactory deficit by the age of 6 months which correlated with reduced NEP expression in the brain areas involved in olfactory signalling. The aim of this study was to analyse the effect of administration of a histone deacetylase inhibitor, valproic acid (VA), to adult 5xFAD mice on their olfaction and memory as well as on brain morphology and NEP expression in the parietal cortex (PC) and hippocampus (Hip). The data obtained demonstrated that administration of VA to 7-month-old mice (200 mg/kg of body weight) for 28 days resulted in improvement of their memory in the Morris water maze as well as olfaction in the odor preference and food search tests. This correlated with increased expression of NEP in the PC and Hip as well as a reduced number of amyloid plaques in these brain areas. This strongly suggests that NEP can be considered an important therapeutic target not only in AD but also in olfactory loss.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643620","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}

{"title":"Role and Interplay of Different Signaling Pathways Involved in Sciatic Nerve Regeneration","authors":"Saeedeh Zare Jalise,&nbsp;Sina Habibi,&nbsp;Leyla Fath-Bayati,&nbsp;Mohammad Amin Habibi,&nbsp;Shima Ababzadeh,&nbsp;Faezeh Hosseinzadeh","doi":"10.1007/s12031-024-02286-4","DOIUrl":"10.1007/s12031-024-02286-4","url":null,"abstract":"<div><p>Regeneration of the sciatic nerve is a sophisticated process that involves the interplay of several signaling pathways that orchestrate the cellular responses critical to regeneration. Among the key pathways are the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, cyclic adenosine monophosphate (cAMP), and Janus kinase/signal transducers and transcription activators (JAK/STAT) pathways. In particular, the cAMP pathway modulates neuronal survival and axonal regrowth. It influences various cellular behaviors and gene expression that are essential for nerve regeneration. MAPK is indispensable for Schwann cell differentiation and myelination, whereas PI3K/AKT is integral to the transcription, translation, and cell survival processes that are vital for nerve regeneration. Furthermore, GTP-binding proteins, including those of the Ras homolog gene family (Rho), regulate neural cell adhesion, migration, and survival. Notch signaling also appears to be effective in the early stages of nerve regeneration and in preventing skeletal muscle fibrosis after injury. Understanding the intricate mechanisms and interactions of these pathways is vital for the development of effective therapeutic strategies for sciatic nerve injuries. This review underscores the need for further research to fill existing knowledge gaps and improve therapeutic outcomes.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600644","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}