Frontiers in Molecular Neuroscience最新文献

{"title":"Peripheral gene dysregulation in Negr1-deficient mice: insights into possible links with affective behavior.","authors":"Abdulkadir Yusif Maigoro, Jangrae Kim, Seoyeon Cho, Ara Yoo, Soojin Lee","doi":"10.3389/fnmol.2025.1602201","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1602201","url":null,"abstract":"<p><strong>Introduction: </strong>Neuronal growth regulator 1 (NEGR1) is a brain-enriched membrane protein with mild expression in peripheral tissues such as adipose tissue and skeletal muscle. Genome-wide association studies have implicated NEGR1 as a risk factor for human diseases including obesity, autism, and depression, but its molecular function remains poorly understood.</p><p><strong>Methods: </strong>To explore NEGR1's role in peripheral-to-brain communication, we conducted RNA-seq analysis on four peripheral tissues-intestine, skeletal muscle, liver, and epididymal white adipose tissue-collected from <i>Negr1</i> knockout mice. Differentially expressed genes (DEGs) were identified and subjected to Gene Ontology (GO) enrichment analyses.</p><p><strong>Results: </strong>The DEG analysis revealed dysregulation of ion channels and transporters, potentially contributing to AP-1-mediated inflammatory responses in peripheral tissues. Additionally, interleukin (IL)-17 signaling emerged as a key pathway that may mediate systemic inflammation in <i>Negr1</i>-deficient mice.</p><p><strong>Discussion: </strong>These findings suggest a novel role for NEGR1 in modulating peripheral inflammatory responses and support the hypothesis that peripheral immune dysregulation may contribute to depressive-like behaviors in <i>Negr1</i>-deficient mice. This work enhances our understanding of NEGR1's function in peripheral tissues and its possible involvement in peripheral-central immune crosstalk relevant to psychiatric disorders.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1602201"},"PeriodicalIF":3.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of the chaperonin TCP-1 ring complex in protein aggregation and neurodegeneration.","authors":"Vanlalrinchhani Varte, Diego E Rincon-Limas","doi":"10.3389/fnmol.2025.1617771","DOIUrl":"https://doi.org/10.3389/fnmol.2025.1617771","url":null,"abstract":"<p><p>The chaperonin TCP-1 ring complex (TRiC), also known as chaperonin-containing TCP-1 (CCT) complex, plays a crucial role in protein folding and quality control within the cell. Comprising eight distinct subunits (CCT1 - CCT8), TRiC assists in the folding of a wide range of client proteins, ensuring their proper conformation and functionality. This mini review explores the assembly, structure, and cellular functions of TRiC and discusses its involvement in protein aggregation and neurodegenerative diseases. We emphasize the emerging role of CCT2 in modulating the formation of abnormal amyloid aggregates, including amyloid beta, tau, and polyglutamine (polyQ) deposits, which are central to the pathogenesis of various neurological conditions. Lastly, we provide evidence supporting the neuroprotective role of CCT2 <i>in vivo</i> and also highlight therapeutic implications and key unresolved questions in the field, offering a foundation for new research opportunities.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1617771"},"PeriodicalIF":3.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRP channels in mammalian hearing loss.","authors":"Zhidong Zhang, Baoshan Wang","doi":"10.3389/fnmol.2025.1626640","DOIUrl":"10.3389/fnmol.2025.1626640","url":null,"abstract":"<p><p>Hearing loss, a common sensory disorder, significantly diminishes quality of life and can stem from diverse causes, including genetic predispositions, aging, noise exposure, and ototoxic medications. Recent research has highlighted the involvement of transient receptor potential (TRP) channels in auditory function and hearing loss. This review offers a comprehensive overview of the current knowledge regarding the roles of TRP channels in mammalian auditory function and hearing loss. By synthesizing the latest research findings, this review aims to elucidate the complex interplay between TRP channels and auditory function, emphasizing their significance in the pathogenesis of hearing loss and identifying potential targets for future therapeutic interventions.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1626640"},"PeriodicalIF":3.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-mediated miRNA delivery: a molecular switch for reshaping neuropathic pain therapy.","authors":"Ziqing Wei, Chunhui Guo, Hang Zhou, Yanling Wu, Xudong Zhou, Jibing Chen, Fujun Li","doi":"10.3389/fnmol.2025.1625943","DOIUrl":"10.3389/fnmol.2025.1625943","url":null,"abstract":"<p><p>Neuropathic pain (NP) is a chronic condition caused by nerve injury or disease. It remains a therapeutic challenge because conventional drugs have limited efficacy and cause adverse effects. Exosomes, with the ability to cross the blood-brain barrier, low immunogenicity, and tissue-homing capacity, have emerged as promising nanovehicles for precise microRNA (miRNA) delivery to modulate key NP pathologies such as neuroinflammation, neuronal hyperexcitability, mechanical allodynia, and thermal hyperalgesia. In this review, we highlight recent advances in exosome-mediated miRNA therapy for NP. We also elucidate the molecular mechanisms and unique advantages of exosomes as both delivery platforms and intrinsic therapeutic agents. We synthesize evidence from preclinical models and initial clinical-stage studies, addressing translational challenges in scalable production and targeted delivery. Through sustained innovation and multidisciplinary collaboration, exosome-based miRNA delivery systems demonstrate transformative potential to overcome current therapeutic limitations, enabling novel NP management strategies.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1625943"},"PeriodicalIF":3.5,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12271170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognition of the microbial metabolite <i>p</i>-cresol in autism spectrum disorder: systematic review and meta-analysis.","authors":"María Isabel Serrano-Tomás, Paulina Contreras-Romero, Mara Parellada, Javier Chaves-Cordero, Javier Zamora, Martha Hengst, Patricia Pozo, Rosa Del Campo, Sheyla Guzmán-Salas","doi":"10.3389/fnmol.2025.1576388","DOIUrl":"10.3389/fnmol.2025.1576388","url":null,"abstract":"<p><strong>Introduction: </strong>In recent years, research has focused on the gut-brain axis and its microbial metabolites as potential etiological or physiopathological agents of autism spectrum disorders (ASDs). Elevated levels of the organic compound <i>para</i>-cresol (<i>p</i>-cresol) have been reported in various populations of children with ASD, suggesting that it could be validated as a possible ASD biomarker related to microbiota. The aim of this study was to perform a systematic review of <i>p</i>-cresol in ASD along with a meta-analysis to elucidate the scientific evidence of its potential as a biomarker.</p><p><strong>Methods: </strong>A search was performed in the PubMed, Web of Science and Scopus databases in May 2024. The Axis critical appraisal tool was used to evaluate the methodological quality of the studies included in the review. Three independent reviewers examined the identified records and performed data extraction.</p><p><strong>Results: </strong>The systematic review yielded 15 articles, of which only 6 were ultimately used for the meta-analysis. Urinary <i>p</i>-cresol levels were significantly higher in those with ASD than in healthy controls, whereas no significant differences were observed in feces.</p><p><strong>Conclusion: </strong>This meta-analysis validates that in ASD an increased level of <i>p</i>-cresol is detected in urine, which could represent a marker of microbiota evolution assessment in the pathogenesis of the disease. However, further research is needed to determine whether there is a causal relationship between the role of this metabolite and the pathophysiology of ASD and to validate its clinical utility.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1576388"},"PeriodicalIF":3.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The neurological pathology of peroxisomal ACBD5 deficiency - lessons from patients and mouse models.","authors":"Michael L Dawes, Jim P Haberlander, Markus Islinger, Michael Schrader","doi":"10.3389/fnmol.2025.1602343","DOIUrl":"10.3389/fnmol.2025.1602343","url":null,"abstract":"<p><p>The absence or dysfunction of the peroxisomal membrane protein Acyl-CoA Binding Domain-Containing Protein 5 (ACBD5) is the cause of the most recently discovered peroxisomal disorder \"Retinal Dystrophy with Leukodystrophy\" (RDLKD). ACBD5 is a tail-anchored protein, anchored by its C-terminus into the peroxisomal membrane; hence, the bulk of its amino acid sequence faces the cytosol. With respect to ACBD5's molecular functions, RDLKD is unique since it is not only an accessory protein for the import of very-long-chain fatty acids (VLCFAs) into peroxisomes but also the first identified peroxisomal tethering protein facilitating membrane contacts with the endoplasmic reticulum (ER). Consequently, RDLKD is neither a peroxisomal biogenesis disorder nor single enzyme deficiency, since a deficiency in ACBD5 likely affects several aspects of peroxisomal function including VLCFA degradation, ether lipid synthesis, docosahexaenoic acid synthesis but also the transfer of membrane lipids from the ER to peroxisomes. Hence, RDLKD appears to be a multifactorial disorder leading to a mosaic pathology, combining symptoms caused by the disruption of several pathways. In this review, we will highlight recent findings obtained from case reports of RDLKD patients as well as insights from ACBD5-deficient mouse models to better understand its complex retinal and brain pathology. Moreover, we will discuss the possible contribution of the different dysregulated metabolites in the neurological pathogenesis of this latest peroxisomal disorder.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1602343"},"PeriodicalIF":3.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Come as you R(NA): post-transcriptional regulation will do the rest.","authors":"Oriane Mauger, Michael A Kiebler, Clémence Bernard","doi":"10.3389/fnmol.2025.1644067","DOIUrl":"10.3389/fnmol.2025.1644067","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1644067"},"PeriodicalIF":3.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259662/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of heme oxygenase-1 regulation of ferroptosis in vascular dementia.","authors":"Xin-Yi Zou, Luo-Yang Cai, Jin Zhang, Ying Yuan, Jie Song, Zhao-Duan Hu, Xiao-Feng Ruan, Rui Peng, Xiao-Ming Zhang","doi":"10.3389/fnmol.2025.1585079","DOIUrl":"10.3389/fnmol.2025.1585079","url":null,"abstract":"<p><p>Vascular dementia (VaD) is a neurodegenerative disorder characterized by chronic oxygen insufficiency, leading to the generation of oxygen-free radicals, inflammatory responses, disturbances in iron metabolism, lipid peroxidation, and other pathological changes that disrupt intracellular homeostasis. These processes ultimately lead to neuronal death and cognitive dysfunction. Normal neurological functions depend on the capacity of the iron homeostatic system to regulate the balance of oxidative states. Imbalances in iron metabolism render nerve cells highly susceptible to cell death induced by iron accumulation. Ferroptosis is a process in which iron catalyzes the peroxidation of unsaturated fatty acid-rich lipids, with ferrous iron or lipoxygenase acting as catalysts and ultimately resulting in cellular demise. Heme oxygenase-1 (HO-1) is a critical enzyme involved in the cellular response to oxidative stress and is essential for regulating signaling pathways linked to iron-mediated cell death. It protects neuronal cells by mitigating oxidative stress, reducing inflammation, and enhancing mitochondrial function, thereby alleviating cerebrovascular injury and slowing the progression of VaD. This paper provides a theoretical framework for understanding and potentially treating VaD-related neuronal injury through the investigation of ferroptosis mechanisms, the biological functions of HO-1, and its role in regulating ferroptosis.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1585079"},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential anti-seizure effects of Astaxanthin-loaded nanostructured lipid carriers in rat model of status epilepticus.","authors":"Sherien E Khalaf, Mohammad Al Masri, Ghaleb Oriquat, Maher A Kamel, Nagwa M Assem, Suzan M Abdel-Tawab, Samar S Elblehi, Shimaa A Mahmoud","doi":"10.3389/fnmol.2025.1613893","DOIUrl":"10.3389/fnmol.2025.1613893","url":null,"abstract":"<p><strong>Introduction: </strong>Epilepsy is a common neurological disorder; seizures and hyperexcitability are its defining features in the central nervous system (CNS). The condition known as status epilepticus (SE) can be fatal, as it involves seizures occurring. Epilepsy is typically treated with antiepileptic drugs (AEDs) like carbamazepine (CBZ). The present study aimed to establish a rat model of SE-like disease using the LiCl-pilocarpine and then utilize these rat models to evaluate the therapeutic potential of AST and/or CBZ in a solution form or loaded on NLCs via intranasal administration. Additionally, to investigate the potential molecular targets of AST and AST + CBZ-nanoformulations.</p><p><strong>Methods: </strong>After the treatment was completed, the rats underwent behavioral tests, including the rotarod and Morris Water Maze (MWM). They are then sacrificed and their brains were dissected to obtain the cerebral cortex and hippocampus for the assessment of neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and dopamine; gene expression of GABA type A (GABAA) receptors subunits and gephyrin; indicators of inflammation like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and High-Mobility Group Box 1 (HMGB1); antioxidant markers, including nuclear factor transcription factor E2-related factor 2 (Nrf2) and hem oxygenase-1 (HO-1).</p><p><strong>Results: </strong>The rats treated with the combination of AST and CBZ in nano-formulations seeing the best results.</p><p><strong>Discussion: </strong>Astaxanthin (AST) may reduce epilepsy-induced oxidative stress and neuronal cell death in the brain. Nano lipid carriers (NLCs) serve as better drug delivery carriers for lipophilic drugs such as CBZ and AST. AST exhibited potential anti-epileptic effects on its own, particularly as NLC-nanoformulations and when combined with conventional AEDs (CBZ).</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1613893"},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding pain chronification: mechanisms of the acute-to-chronic transition.","authors":"Shunwei Zhang, Youzhi Ning, Yiyi Yang, Guo Mu, Yongkui Yang, Changhe Ren, Changli Liao, Cehua Ou, Yue Zhang","doi":"10.3389/fnmol.2025.1596367","DOIUrl":"10.3389/fnmol.2025.1596367","url":null,"abstract":"<p><p>Pain chronification is a multidimensional and active pathophysiological process, not merely a consequence of prolonged nociception. This review proposes a four-domain mechanistic framework to elucidate the transition from acute to chronic pain. At the molecular-cellular level, persistent neuroinflammation-driven by activated glial cells and pro-inflammatory mediators such as TNF-α and IL-1β-leads to peripheral and central sensitization through enhanced excitability and ion channel dysregulation. In parallel, epigenetic mechanisms such as DNA methylation and histone modifications alter the expression of pain-related genes (e.g., SCN9A, BDNF), establishing a long-term transcriptional predisposition to chronic pain. These changes converge on maladaptive neural plasticity, characterized by aberrant synaptic strengthening, cortical map reorganization, and disrupted functional connectivity, which embed pain into persistent network states. Moreover, psychosocial factors-including catastrophizing, affective distress, and impaired top-down regulation-amplify pain through feedback loops involving the prefrontal cortex, amygdala, and hypothalamic-pituitary-adrenal (HPA) axis. By integrating these four interconnected domains, we highlight critical windows for mechanism-informed, temporally targeted interventions that may interrupt pain chronification and enable a shift toward proactive, personalized pain prevention.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1596367"},"PeriodicalIF":3.5,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12241141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}