Journal of Molecular Neuroscience最新文献

{"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":"Lack of Association between BDNF rs6265 and Multiple Sclerosis: A Case–Control Study","authors":"Ioannis Liampas,&nbsp;Daniil Tsirelis,&nbsp;Metaxia Dastamani,&nbsp;Stavroula-Ioanna Pariou,&nbsp;Maria Papasavva,&nbsp;Martha-Spyridoula Katsarou,&nbsp;Annia Tsolakou,&nbsp;Aristidis Tsatsakis,&nbsp;Dimitrios P. Bogdanos,&nbsp;Nikolaos Drakoulis,&nbsp;Efthimios Dardiotis,&nbsp;Vasileios Siokas","doi":"10.1007/s12031-024-02301-8","DOIUrl":"10.1007/s12031-024-02301-8","url":null,"abstract":"<div><h3>Background and Objectives</h3><p>Data on the association between BDNF rs6265 and multiple sclerosis (MS) are scarce and heterogeneous.</p><h3>Materials and Methods</h3><p>We undertook a case–control study design. Newly diagnosed individuals with MS based on the 2017 revision of the McDonald criteria were recruited from the Neurology Department of the General University Hospital of Larissa. Healthy controls with a free medical and family history were also recruited. The relationship between BDNF rs6265 and MS was defined as the primary outcome. The association between rs6265 and age of MS onset, spinal lesions, and clinical manifestations at the time of MS onset were defined as the secondary outcomes.</p><h3>Results</h3><p>We genotyped a total of 200 patients with MS and 205 healthy controls, yielding a sample power of approximately 80%. BDNF rs6265 was in Hardy–Weinberg Equilibrium among healthy participants (p = 0.64). No significant relationship was revealed between rs6265 and MS [log-additive OR = 0.83 (0.57,1.21), over-dominant OR = 0.73 (0.48,1.14), recessive OR = 1.24 (0.37,4.12), dominant OR = 0.77 (0.50,1.17), co-dominant OR1 = 0.74 (0.48,1.14) and co-dominant OR2 = 1.13 (0.34,3.80)]. Additionally, rs6265 was unrelated to the age of MS onset according to both unadjusted and sex-adjusted cox-proportional models. Finally, rs6265 was not associated with the presence of spinal lesions (cervical or thoracic) at MS onset, according to both unadjusted and age and sex-adjusted logistic regression models.</p><h3>Conclusions</h3><p>We failed to establish an association between BDNF rs6265 and the risk of MS, the age of onset, the presence of spinal lesions, and the clinical manifestations at the onset.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"75 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845020","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":"Advanced Glycation End Products in Neurodegenerative Diseases","authors":"Cibin T. Raghavan","doi":"10.1007/s12031-024-02297-1","DOIUrl":"10.1007/s12031-024-02297-1","url":null,"abstract":"<div><p>Advanced glycation end products (AGEs) have attracted interest as therapeutic targets for neurodegenerative diseases. AGEs facilitate the onset and progression of various neurogenerative disorders due to their ability to promote cross-linking and aggregation of proteins. Further, the interaction between AGEs and receptor for AGEs (RAGE) activates neuroinflammatory, oxidative stress and excitotoxicity processes that contribute to neuronal cell death. Various therapeutic efforts have targeted lowering the production of AGEs, inhibiting RAGE or inhibiting some of the processes of the AGE-RAGE axis as potential treatments for these disorders. Whereas effective treatments for many neurodegenerative disorders remain elusive, such efforts offer promise to slow the progression of diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD).</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798260","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":"Effect of Prednisolone on Clinical and Cytokine mRNA Profiling in Complex Regional Pain Syndrome","authors":"Jayantee Kalita,&nbsp;Ruchi Shukla,&nbsp;Prakash C. Pandey","doi":"10.1007/s12031-024-02290-8","DOIUrl":"10.1007/s12031-024-02290-8","url":null,"abstract":"<div><p>The cardinal clinical features of complex regional pain syndrome type I (CRPS-I) are pain, edema, autonomic changes, and limitation of motoric movement, which may indicate the role of inflammation and cytokines. We report the effect of prednisolone on the clinical severity and mRNA profiling of proinflammatory (tumor necrosis factor (TNF)-α and interleukin (IL)-2) and anti-inflammatory cytokines (IL-10 and transforming growth factor (TGF)-β) in the patient with CRPS-I. Thirty-nine patients with CRPS-I of shoulder joint were enrolled. Their CRPS, Visual Analog Scale (VAS) and Daily Sleep Interference Scale (DSIS) scores were recorded. TNF-α, IL-2, IL-10, and TGF-β gene expressions at mRNA of whole blood were measured by reverse transcriptase polymerase chain reaction. Patients were randomized to prednisolone 20 mg or 40 mg using 1: 1 randomization. The primary outcome was change in VAS score, and secondary outcomes were change in CRPS and DSIS scores at 1 month. Side effects were noted. The patients had increased expressions of TNF-α (<i>p</i> &lt; 0.001) and IL-2 (<i>p</i> &lt; 0.001) and reduced IL-10 (<i>p</i> &lt; 0.01) mRNA compared to the healthy controls. The baseline characteristics were matched between the two treatment arms. At 1 month, CRPS, VAS, and DSIS scores improved significantly compared to baseline, which paralleled with improvement in IL-10 (<i>p</i> &lt; 0.032) and reduction in TNF-α (<i>p</i> = 0.046). The improvement in clinical and biomarkers was similar in prednisolone 20 mg and 40 mg arms. None had to be withdrawn due to severe side effects. Future study in larger cohort may validate these findings.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778361","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":"Investigation of Association Between Expression of DYX1C1, KIAA0319, and ROBO1 Genes and Specific Learning Disorder in Children and Adolescents","authors":"Burcu Bayyurt,&nbsp;Nil Özbilüm Şahin,&nbsp;Cansu Mercan Işık","doi":"10.1007/s12031-024-02288-2","DOIUrl":"10.1007/s12031-024-02288-2","url":null,"abstract":"<div><p>Specific learning disorder (SLD) is prevalent worldwide and is a complex disorder with variable symptoms and significant differences among individuals. Epigenetic markers may alter susceptibility to neurodevelopmental disorders (NDDs). Aberrant expression of protein-coding (mRNA) genes in this pathology shows that the detection of epigenetic molecular biomarkers is of increasing importance in the diagnosis and treatment of individuals with SLD. We compared gene expression level of <i>dyslexia susceptibility 1 candidate gene 1</i> (<i>DYX1C1</i>), <i>dyslexia-associated protein KIAA0319</i> (<i>KIAA0319</i>), and <i>roundabout guidance receptor 1</i> (<i>ROBO1</i>) between children with SLD and healthy children by performing quantitative polymerase chain reaction (qPCR). In addition, we evaluated these gene expressions of severe children with SLD compared to non-severe and male SLD children compared to females. The expression of the <i>DYX1C1</i>, <i>KIAA0319</i>, and <i>ROBO1</i> genes was statistically significantly upregulated in children with SLD (<i>P</i> &lt; 0.05*). <i>DYX1C1</i> was also upregulated in severe SLD children (<i>P</i> = 0.03*). In addition, <i>KIAA0319</i> and <i>ROBO1</i> genes were differentially expressed in male SLD children compared to females (<i>P</i> &lt; 0.05*). Furthermore, we found that <i>DYX1C1</i> and <i>ROBO1</i> genes significantly affect the likelihood of the SLD (respectively, <i>P</i> &lt; 0.001** and <i>P</i> = 0.007*). We expect that the findings provided from this study may contribute to the determination expression level of the relevant genes in the diagnosis, prognosis, and treatment of SLD. In addition, our findings could be a guide for future epigenetics studies on the use of the <i>DYX1C1</i>, <i>KIAA0319</i>, and <i>ROBO1</i> in therapeutic applications in the SLD.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"74 4","pages":""},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611764","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}