Frontiers in Molecular Neuroscience最新文献

{"title":"Correction: Prenatal and neonatal housing conditions affect anxiety-like behavior in adulthood in rats and interact with brain-derived neurotrophic factor (BDNF) Val66Met to alter expression of BDNF and stress markers in the ventral hippocampus.","authors":"Maarten van den Buuse, Michelle Corrone, Emily J Jaehne, Veronica Begni, Alessia Marchesin, Marco A Riva","doi":"10.3389/fnmol.2026.1992919","DOIUrl":"10.3389/fnmol.2026.1992919","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fnmol.2026.1844602.].</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1992919"},"PeriodicalIF":4.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13656404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181155","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":"From dynamic condensates to pathological assemblies: the phase behavior of tau and <i>α</i>-synuclein.","authors":"Suelen Camargo, Kevin Novelo, Scott D Ryan","doi":"10.3389/fnmol.2026.1965177","DOIUrl":"https://doi.org/10.3389/fnmol.2026.1965177","url":null,"abstract":"<p><p>Neurons rely on precise protein folding, trafficking, and turnover to maintain synaptic function. Disruption of proteostasis promotes misfolded proteins that impair axonal transport, mitochondrial function, and signalling, contributing to neuronal loss. Although neurodegeneration has traditionally focused on stable amyloid deposits, many disease-associated proteins contain intrinsically disordered regions (IDRs) that can organize through liquid-liquid phase separation (LLPS). LLPS concentrates proteins and nucleic acids into dynamic condensates that regulate cellular processes, but these adaptive interactions can also promote condensate aging and less reversible, aggregation-prone states. Here, we review how sequence-encoded properties of tau and α-synuclein (α-syn) link physiological condensation to pathological protein assembly, while emphasizing that LLPS and amyloid formation are related but not obligatorily linked.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1965177"},"PeriodicalIF":4.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166634","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":"Beyond development: LINX/Islr2 expression and TrkA interaction in the adult nervous system under neuroinflammatory challenge.","authors":"Pamela Rosso, Elena Fico, Viviana Triaca, Annamaria Di Criscio, Ari-Pekka Koivisto, Katja Kuokkanen, Mikko Ares, Kaisa Auvinen, Andrii Domanskyii, Johanna Kela, Carina Stenfors, Paola Tirassa","doi":"10.3389/fnmol.2026.1863350","DOIUrl":"10.3389/fnmol.2026.1863350","url":null,"abstract":"<p><strong>Introduction: </strong>LINX, also known as immunoglobulin superfamily containing leucine-rich repeat 2 (Islr2), was identified as a TrkA pathway component and demonstrated to modulate the NGF/TrkA-mediated axonal growth, guidance, and branching during development. However, there is limited information on LINX expression in the adult nervous system, and the possible functions of LINX in mature neurons remain unexplored. These two questions are addressed by the present study, which first investigates LINX expression in the adult spinal cord (SC), dorsal root ganglia (DRG), and cerebral cortex (Cx), and subsequently explores LINX/TrkA functions using the DRG organ culture model.</p><p><strong>Methods: </strong>Different commercially available anti-LINX antibodies were tested, and the most selective antibody was used to investigate LINX expression in the SC, Cx, and DRG of healthy rats, and to explore the LINX/TrkA action in DRG organ cultures using a model of neuroinflammation/injury induced by lipopolysaccharides (LPS). The LINX/TrkA interaction was demonstrated by immunoprecipitation in the Cx of healthy and LPS-treated rats. The DRG from healthy and LPS-treated rats were dissected and cultured in the presence of anti-LINX, with or without stimulation using NGF, and a TrkA selective inhibitor. TrkA phosphorylation levels and the expression of the axonal growth marker GAP43 were analyzed by bio-molecular assays and confocal immunofluorescence microscopy.</p><p><strong>Results: </strong>The WB analysis shows that LINX is expressed in the adult central and peripheral nervous systems, and the immunoprecipitation analysis demonstrates LINX and TrkA interaction in the Cx of both adult healthy and LPS-treated rats. <i>In vitro</i> experiments using an LPS-DRG model confirm the association between LINX and TrkA. However, it was found that while anti-LINX administration abolishes the effects of NGF and TrkA activation in LPS-DRG, it results in GAP43 increase in the presence of a TrkA inhibitor.</p><p><strong>Discussion: </strong>Our study confirms that LINX is expressed in the adult central nervous system and demonstrates that the LINX/TrkA interaction is maintained following LPS-induced systemic inflammation. Moreover, our findings that antibody-mediated perturbation of endogenous LINX is associated with the modulation of axonal growth markers in adult LP-DRG cultures, in serum-free conditions and/or in the presence of a TrkA inhibitor, suggest a potential role for LINX in regulating neurotrophin-dependent responses in injured adult neurons.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1863350"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136162","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":"Garlic-derived bioactive components in neuropathic pain: molecular mechanisms and therapeutic promise.","authors":"Asif Ali, Sorimuthu Revathi, Koilmani Emmanuvel Rajan, Chin Kun Wang, Subramanian Thangaleela","doi":"10.3389/fnmol.2026.1886063","DOIUrl":"10.3389/fnmol.2026.1886063","url":null,"abstract":"<p><p>Neuropathic pain is a chronic condition associated with maladaptive changes in nociceptive pathways, driven by oxidative stress, mitochondrial impairment, neuroinflammation, ion channel dysfunction, and apoptotic dysregulation. Current pharmacological therapies often provide limited relief but with adverse effects highlighting the need for more safer therapeutic approaches. Garlic (<i>Allium sativum</i>) and its bioactive organosulfur compounds including allicin, S-allyl cysteine, diallyl disulfide, diallyl trisulfide have gained increasing attention for their neuroprotective potential. This review summarizes the mechanistic role of garlic-derived compounds in neuropathic pain modulation, focusing on their antioxidant, anti-inflammatory, anti-apoptotic, and mitochondrial-stabilizing properties. These bioactives regulate key signaling pathways such as NF-κB, Nrf2/HO-1, PI3K/Akt, and JNK, while also modulating TRPV1 and TRPA1 ion channels involved in nociception and central sensitization furthermore, garlic compounds enhance endogenous antioxidant defense, preserve mitochondrial bioenergetics, and inhibit caspase-mediated neuronal apoptosis, thereby contributing to neuroprotection. Despite promising preclinical evidence, challenges such as variability in garlic preparations, limited clinical studies, and insufficient pharmacokinetic data remain. Overall, garlic-derived compounds represent a promising complementary strategy for neuropathic pain management, warranting further standardized clinical investigations to validate their therapeutic efficacy and safety.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1886063"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136173","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":"Tanshinone IIA and sodium tanshinone IIA sulfonate in ischemic stroke: evidence, exposure, and translational readiness.","authors":"Aiyue Fan, Weiting Chen, Min Tang, Yangtian Ye, Yaling Jin","doi":"10.3389/fnmol.2026.1959038","DOIUrl":"10.3389/fnmol.2026.1959038","url":null,"abstract":"<p><p>Ischemic stroke remains a major cause of death and long-term disability despite reperfusion therapy. Tanshinone IIA (Tan IIA), a lipophilic diterpene quinone, and sodium tanshinone IIA sulfonate (STS), its water-soluble sulfonated derivative, show broad activity in experimental cerebral ischemia. They are often treated as interchangeable despite differences in formulation and exposure. We critically reviewed representative pharmacological, preclinical, formulation, and clinical evidence through 28 July 2026. We distinguished active entity, formulation, causal support, replication, exposure linkage, treatment window, and patient-centered relevance. Reported effects span oxidative and mitochondrial injury, endothelial barrier failure, neuroinflammation, regulated cell death, metabolism, and repair. Most pathway claims, however, rely on single laboratories, early dosing, young healthy rodents, short follow-up, or surrogate outcomes. Human evidence comprises one 42-patient STS-plus-rt-PA trial and a 2025 meta-analysis of 22 trials involving 2,289 participants. These findings suggest short-term signals but do not establish benefits for ordinal disability, survival, recurrent stroke, or uncommon bleeding. An injectable product and human plasma pharmacokinetic methods make STS more operationally tractable; superior efficacy remains unproven. Progression should require a fixed product, exposure-linked target engagement, durable benefit in aged and comorbid reperfusion models, and independent multicenter validation. Biological plausibility remains substantially stronger than translational readiness.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1959038"},"PeriodicalIF":4.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643747/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136221","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":"Multiple subject tracking in long-term, behavioral studies of rodents.","authors":"Bartosz Zglinicki","doi":"10.3389/fnmol.2026.1960212","DOIUrl":"10.3389/fnmol.2026.1960212","url":null,"abstract":"","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1960212"},"PeriodicalIF":4.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108412","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":"Expression and role of HSPA5 in environmental toxin-induced neurological disorders.","authors":"Yurong Wang, Yang Lv, Ruidong Zhao, Xin Guo, Jing Gao, Tong Wang, Dongmei Yao, Xin Li, Bingchun Liu, Jianlong Yuan","doi":"10.3389/fnmol.2026.1964213","DOIUrl":"https://doi.org/10.3389/fnmol.2026.1964213","url":null,"abstract":"<p><p>HSPA5 is a member of the HSP70 family of heat shock proteins (HSPs) and functions as a chaperone protein within the endoplasmic reticulum (ER). It plays a role in maintaining ER homeostasis, assists in correct protein folding, and triggers the unfolded protein response. Environmental toxins-such as heavy metals, microplastics (MPs), and air pollutants-can cause cellular damage. These toxins can trigger ER stress, resulting in the buildup of proteins that are misfolded or not properly folded, which in turn upregulates HSPA5 expression. Moderate activation of HSPA5 serves as a protective mechanism aimed at restoring protein homeostasis and promoting cell survival; however, sustained and severe ER stress may cause HSPA5 to malfunction, ultimately leading to the activation of the apoptotic pathway and resulting in cell death. Furthermore, HSPA5-mediated mechanisms are closely associated with the prodromal initiation and subsequent escalation of neurodegenerative syndromes. This article focuses on the role of HSPA5 in environmental toxin-induced neurotoxicity and neurodegenerative diseases, with the aim of investigating changes in HSPA5 expression and its regulatory functions in neurotoxicity, thereby providing new strategies for the study of environment-related neurodegenerative diseases.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1964213"},"PeriodicalIF":4.4,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108376","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 aryl hydrocarbon receptor is expressed in non-sensory cells in the cochlea and regulates hair cell survival.","authors":"Sujata Pandey, Brandon C Cox","doi":"10.3389/fnmol.2026.1943479","DOIUrl":"https://doi.org/10.3389/fnmol.2026.1943479","url":null,"abstract":"<p><p>Damage or loss of hair cells, the sensory cells for hearing, is caused by ototoxic drugs or acoustic trauma, and results in permanent hearing loss because the adult cochlea lacks regenerative capacity. Therefore, identifying pathways that regulate hair cell survival is critical. Here we investigate a novel pathway, aryl hydrocarbon receptor (AhR) signaling in the cochlea. We demonstrate for the first time, the expression pattern of AhR in the cochlea under physiological conditions and after exposure to neomycin or noise. Under physiological conditions, AhR was strongly expressed in glia surrounding spiral ganglion neurons with low expression in the organ of Corti. Following neomycin treatment or noise exposure, AhR expression increased in supporting cells suggesting a dynamic response to hair cell injury. This hair cell to supporting cell communication is mediated in part by purinergic signaling, since treatment with ATP mimicked the effect of neomycin, and treatment with the purinergic antagonist suramin eliminated AhR upregulation. In addition, deletion of <i>AhR</i> from the organ of Corti significantly increased hair cell loss after neomycin treatment compared to controls with normal <i>AhR</i> levels. Our findings establish AhR as a cellular biosensor in supporting cells which is upregulated during hair cell injury to regulate the survival of hair cells.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1943479"},"PeriodicalIF":4.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108363","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":"Assessment of microexon-associated junction usage in Parkinson's disease and spinocerebellar Ataxia type 3.","authors":"Kira Mehnert, Jeannette Hübener-Schmid, Jakob Admard, Vladislav Lysenkov, German Demidov, Chrisovalantou Huridou, Jonasz Jeremiasz Weber, Olaf Riess, Nicolas Casadei","doi":"10.3389/fnmol.2026.1872346","DOIUrl":"https://doi.org/10.3389/fnmol.2026.1872346","url":null,"abstract":"<p><strong>Background: </strong>Microexons are short exonic sequences of 3-30 nucleotides that undergo alternative splicing and have been implicated in several neurodevelopmental disorders. However, their contribution to neurodegenerative diseases remains insufficiently characterized.</p><p><strong>Methods: </strong>We analyzed microexon-associated junction usage in the frontal cortex of Parkinson's disease (PD) patients and in the cerebellum of Spinocerebellar Ataxia Type 3 (SCA3) patients using deep RNA-Sequencing of human postmortem brain tissue and corresponding SH-SY5Y cellular models. Microexon-associated junction usage was quantified based on splice junction reads derived from STAR alignments, followed by statistical testing with false discovery rate (FDR) correction for multiple testing and visualization using Sashimi plots. Selected candidate events in the cellular datasets were assessed by PCR.</p><p><strong>Results: </strong>Across all datasets, 19 microexon-associated junction candidate events were identified but did not survive FDR correction. Human brain tissue exhibited substantially more detectable microexons compared to cellular models, which may reflect differences in splicing complexity between differentiated tissue and neuroblastoma-derived cells. While visual inspection suggested that effect sizes were generally small and variable across samples, the majority of microexon-containing genes were expressed in both systems. PCR confirmed detection of the selected microexons but did not validate differences in microexon-associated junction usage between experimental groups.</p><p><strong>Conclusion: </strong>Our findings provide an overview of microexon landscapes in PD and SCA3 and an exploratory statistical analysis. Although large and consistent disease-specific patterns of microexon-associated junction usage were not observed, our findings suggest that microexon regulation in neurodegeneration may involve subtle and context-dependent alterations that warrant further investigation in larger cohorts.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1872346"},"PeriodicalIF":4.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108386","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":"3-hydroxy-3-methylbutyrate (3H3MB) suppresses glioma growth and extends survival in mice.","authors":"Rizwan Khan, Xingzi Lin, Francesco Marrocco, Ottavia Giampaoli, Alice Reccagni, Javeria Maqbool, Fabio Sciubba, Adriano Patriarca, Michele De Rosa, Alfredo Miccheli, Gabriele Favaretto, Fabrizio Antonangeli, Cristina Limatola, Giuseppina D'Alessandro","doi":"10.3389/fnmol.2026.1917452","DOIUrl":"https://doi.org/10.3389/fnmol.2026.1917452","url":null,"abstract":"<p><p>Glioblastoma (GBM) is the most aggressive primary malignancy of the central nervous system, characterized by poor prognosis, limited therapeutic options, and a high rate of recurrence. A major contributor to its dismal clinical outcome is the highly invasive nature of glioblastoma cells, which infiltrate surrounding healthy brain parenchyma, precluding complete surgical resection and promoting therapeutic resistance. Emerging evidence suggests that the gut microbiota influences glioblastoma progression via modulation of neurotransmitter signaling and immune responses, and through alteration of microbial composition and metabolite production that impact tumor development. Building on our prior work demonstrating the relevance of the gut-brain axis in both physiological and glioma contexts, we identified a significant reduction in fecal levels of 3-hydroxy-3-methylbutyrate (3H3MB), a gut-associated leucine-derived metabolite that is chemically and metabolically distinct from the short-chain fatty acid butyrate, in glioma-bearing mice relative to their pre-tumor state. Given that 3H3MB administration has been reported to attenuate growth and proliferation in carcinoma models, we investigated its potential anti-tumor effects in glioma. <i>In vivo</i>, oral gavage of 3H3MB to glioma-bearing mice resulted in a significant reduction in tumor volume, decreased cellular proliferation, and prolonged overall survival compared to control animals. <i>In vitro</i>, 3H3MB markedly inhibited the proliferation of mouse glioma and human glioblastoma cell lines, modulating cell cycle phases; moreover, the treatment suppressed glioma cell migration and serum-induced invasion. These findings suggest that 3H3MB exerts robust anti-tumor effects in glioma-bearing mice and holds promise as a novel metabolic therapy for glioblastoma, supported by its established clinical evaluation in other pathological conditions.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"19 ","pages":"1917452"},"PeriodicalIF":4.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149108394","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}