NeuroMolecular Medicine最新文献

{"title":"A Slower-Progressing TDP-43 rNLS8 Mouse Model for ALS: Implications for Preclinical and Mechanistic Studies.","authors":"Cyril Jones Jagaraj, Prachi Mehta, Julie Hunter, Julie D Atkin","doi":"10.1007/s12017-025-08871-z","DOIUrl":"10.1007/s12017-025-08871-z","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised by motor neuron degeneration, muscle weakness, paralysis, and eventual death, with TAR DNA-binding protein 43 (TDP-43) pathology observed in almost all cases. Mouse models based on TDP-43 are thus essential for studying ALS and developing therapeutic approaches. The TDP-43 rNLS8 mouse model expresses a human TDP-43 transgene with a mutated nuclear localization sequence (hTDP-43 ΔNLS), but this is normally suppressed by the presence of doxycycline (Dox). Disease is initiated by removal of Dox, which replicates key ALS features, including TDP-43 pathology, neuromuscular junction denervation, motor neuron loss, and reduced survival. However, this model has a rapid disease progression which limits its use for extended preclinical studies and investigation of early disease mechanisms. To overcome these limitations, we explored whether maintaining low Dox concentrations in the diet (10-20 mg/kg) could slow disease progression. Our findings demonstrate that this approach significantly reduced hTDP-43 ΔNLS expression (up to 4.8-fold), which delayed disease onset by four weeks. Disease progression, assessed by rotarod performance, grip strength, and neurological scores, was extended from six to 15 weeks, with a threefold increase in survival. Despite slower progression, at the end stage, mice displayed similar levels of neuroinflammation, motor neuron loss, as Dox off mice. These findings highlight slower-progressing TDP-43 rNLS8 mice as a robust model for preclinical and early disease mechanism studies.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"59"},"PeriodicalIF":3.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874353","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":"An Enigma of Brain Gasotransmitters: Hydrogen Sulfide and Depression.","authors":"Antonello Pinna, Julia Kistowska, Artur Pałasz","doi":"10.1007/s12017-025-08880-y","DOIUrl":"10.1007/s12017-025-08880-y","url":null,"abstract":"<p><p>Depression is a leading global cause of disability. Emerging evidence highlights glutamatergic dysfunction, particularly impaired NMDA receptor signaling, as a key contributor to its neurobiology. Hydrogen sulfide (H₂S), once regarded solely as toxic, is now recognized for its role in regulating synaptic plasticity, inflammation, and neuronal survival. This review synthesizes recent findings on the antidepressant effects of H₂S. In animal models, H₂S administration improves depression-like behaviors while modulating key pathways such as PI3K/AKT/mTOR, Sirt1, and the cGAS-STING pathway. These benefits extend across models of stress, neuropathic pain, diabetes, and sleep deprivation. Among H₂S donors, sodium hydrosulfide (NaHS) demonstrated the most consistent antidepressant effects in preclinical studies. Clinical studies further show that individuals with major depression exhibit lower plasma H₂S levels, with symptom severity inversely correlated to H₂S concentration. Together, these findings support a multifaceted role for H₂S in mood regulation and highlight its promise as both a therapeutic candidate and a potential biomarker in depressive disorders, though translational studies remain needed.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"58"},"PeriodicalIF":3.9,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12334376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799749","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":"Mechanistic Study of Jaceosidin in Regulating Secondary Inflammation After Spinal Cord Injury in Mouse by Inhibiting PKM2 Activity.","authors":"Bin Dai, Zihao Fan, Rui Chen, Xuansen Weng, Run Fang","doi":"10.1007/s12017-025-08877-7","DOIUrl":"10.1007/s12017-025-08877-7","url":null,"abstract":"<p><p>Excessive pro-inflammatory polarization of microglia is a critical driver of secondary inflammation following spinal cord injury (SCI). Jaceosidin, a natural flavonoid with established anti-inflammatory properties, has not been extensively studied in the context of post-SCI inflammation regulation. Given the fundamental role of glycolysis in cellular energy metabolism and its crucial involvement in inflammatory processes, this study investigated the effects of Jaceosidin. We demonstrated that Jaceosidin significantly attenuated the inflammatory response in lipopolysaccharide-stimulated microglia in vitro. Subsequent in vitro and in vivo experiments revealed that Jaceosidin shifted microglial polarization away from the inflammatory state and suppressed glycolytic flux. Mechanistically, Jaceosidin directly targeted and inhibited the activity of pyruvate kinase M2 (PKM2), a key glycolytic enzyme. Intervention with Jaceosidin in a mouse SCI model resulted in reduced microglial activation at the injury site, diminished tissue damage, and significantly improved motor and autonomic nerve function recovery. In conclusion, our findings indicate that Jaceosidin mitigates microglial inflammation and promotes functional recovery after SCI by inhibiting PKM2 activity and dampening glycolysis. As a natural phytochemical derived from traditional Chinese medicine, Jaceosidin presents a promising novel therapeutic strategy for the clinical management of spinal cord injury.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"57"},"PeriodicalIF":3.9,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144789625","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":"Phosphocreatine Mitigates Doxorubicin-Induced Neurotoxicity in Rats by Regulating Mitochondrial Function and Apoptosis via the NF-κB/PGC-1α Pathway.","authors":"Eskandar Qaed, Waleed Aldahmash, Mueataz A Mahyoub, Dalal Sanad Al-Mutairi, Zeyao Tang, Marwan Almoiliqy","doi":"10.1007/s12017-025-08872-y","DOIUrl":"10.1007/s12017-025-08872-y","url":null,"abstract":"<p><p>Doxorubicin (DOX) is an effective chemotherapeutic agent, but its clinical utility is limited by its neurotoxic side effects. This study investigates the neuroprotective effects of phosphocreatine (PCr) against DOX-induced neurotoxicity in Sprague-Dawley rats. Forty rats were randomly assigned to four groups: control, DOX (2 mg/kg), DOX + PCr (20 mg/kg), and DOX + PCr (50 mg/kg). Parameters assessed included body weight, oxidative stress markers (MDA, SOD, GSH), and neurofunctional indicators (nNOS, BDNF). Mitochondrial respiration was evaluated using high-resolution respirometry, measuring state 3 and state 4 respiration, the respiratory control ratio (RCR), and ADP/O ratio. Western blotting was used to analyze apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3, pro-caspase-3, pro-caspase-9, cytochrome c) and signaling molecules (NF-κB, PGC-1α). PCr treatment significantly reduced oxidative stress, as evidenced by lower MDA levels and elevated GSH and SOD. It also modulated apoptotic signaling by decreasing pro-apoptotic proteins (Bax, cleaved caspase-3) and increasing anti-apoptotic Bcl-2. Moreover, PCr enhanced mitochondrial function and biogenesis, while attenuating neuroinflammation through regulation of the NF-κB/PGC-1α pathway. These findings suggest that PCr protects against DOX-induced neurotoxicity by improving mitochondrial bioenergetics, reducing oxidative damage, and inhibiting neuronal apoptosis. PCr may represent a promising therapeutic strategy to mitigate chemotherapy-associated neurotoxicity.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"56"},"PeriodicalIF":3.9,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784889","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":"Platycodin D Attenuates Behavioral Deficits, Amyloid-β Accumulation and Mitochondrial Impairment in AD Models by Inhibiting the cGAS-STING Pathway.","authors":"Chaoyuan Song, Guoliang Yin, Linya Wang, Fengxia Zhang","doi":"10.1007/s12017-025-08878-6","DOIUrl":"10.1007/s12017-025-08878-6","url":null,"abstract":"<p><p>The characteristics of Alzheimer's disease (AD) include behavioral deficits, amyloid-β (Aβ) accumulation, and mitochondrial impairment. Activating of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway significantly increases the production of inflammatory cytokines, which can exacerbate neuroinflammation and accelerate the progression of AD. Platycodin D (PD) has been reported to exhibit anti-inflammatory and neuroprotective properties and is believed to play a role in the progression of AD. Our study aimed to investigate the protective effects of PD in AD and to determine whether these protective effects are associated with the cGAS-STING pathway. In this research, APP/PS1 transgenic mice, an animal model of AD, were administered with PD via intracerebroventricular injection. SHSY5Y cells stably transfected with APPswe gene (APPswe cells) were used as a cell model of AD and treated with PD. Our findings demonstrated that PD attenuated behavioral deficits, Aβ accumulation, mitochondrial impairment, and decreased the expression level of cGAS-STING pathway proteins (cGAS and STING) as well as inflammatory cytokines (TNF-α, IL-1β and IL-18) in AD models. However, cGAMP acts as an agonist of the cGAS-STING pathway upregulated the cGAS-STING pathway and inflammatory cytokines, exacerbated Aβ accumulation and mitochondrial impairment in APPswe cells. In conclusion, our findings suggested that PD attenuated behavioral deficits, Aβ accumulation and mitochondrial impairment in AD models by inhibiting cGAS-STING pathway.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"55"},"PeriodicalIF":3.9,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768820","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 Core Genes Involved in Ischemic Stroke and the Therapeutic Potential of Hyperbaric Oxygen: Insights from Transcriptomic Analysis.","authors":"Yingcun Bao, Xudong Guo, Jinhai Wang, Jihe Kang, Rui Ma, Xiaorong Cheng, Yumei Ma, Yanxia Niu, Wei Zhang, Xiaoling Li","doi":"10.1007/s12017-025-08876-8","DOIUrl":"10.1007/s12017-025-08876-8","url":null,"abstract":"<p><p>Ischemic stroke (IS) is a complex neurological disorder caused by reduced cerebral blood flow, typically resulting in tissue damage due to hypoxia and nutrient deficiency. Hyperbaric oxygen therapy (HBOT) has shown great potential as an adjunctive treatment for IS, though its mechanisms of action are not fully understood. This study employed a middle cerebral artery occlusion (MCAO) mouse model to explore the molecular mechanisms and therapeutic effects of HBOT. Transcriptomic analysis revealed significant changes in gene expression related to ischemia, including differentially expressed genes (DEGs) involved in inflammatory responses, BBB damage, and neural repair, such as Lcn2, Bcl3, Olr1, Pdpn, Gpnmb, and Gfap. HBOT significantly reduced brain damage, modulated the expression of these key genes, and decreased m⁶A methylation levels, thereby affecting post-transcriptional modifications of RNA. These findings provide new insights into the molecular mechanisms of IS and the development of precise treatment strategies, highlighting the potential of HBOT to reduce brain damage and promote neural repair at the molecular level.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"54"},"PeriodicalIF":3.9,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732414","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":"Inflammatory Markers and their Relationship with Cognitive Function in Alzheimer's Disease and Mild Cognitive Impairment. Systematic Review and Meta-Analysis.","authors":"Maria Fernanda Serna, Mildrey Mosquera, Herney Andrés García-Perdomo","doi":"10.1007/s12017-025-08866-w","DOIUrl":"10.1007/s12017-025-08866-w","url":null,"abstract":"<p><p>This study estimates the association between blood levels of inflammatory markers and cognitive function in adults with Alzheimer's disease or mild cognitive impairment. A systematic review and meta-analysis were conducted to synthesize data from studies examining the relationship between blood levels of inflammatory markers and cognitive function in adults with Alzheimer's disease or mild cognitive impairment. The search strategy was applied to the Medline database through MEDLINE (OVID), WEB OF SCIENCE, SCOPUS, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies were selected based on predefined criteria. We included 84 studies in the qualitative synthesis, with 75 incorporated into the meta-analysis. In blood samples, subjects with Alzheimer's disease showed significantly higher concentrations of IL-1β (mean difference 0.46 [95% CI: 0.35, 0.58]), IL-6 (3.41 [3.05, 3.78]), MCP-1 (26.20 [14.57, 37.82]), and TNF-α (6.68 [5.97, 7.39]), along with lower concentrations of IL-8 (- 1.46 [- 1.85, - 1.08]) and IL-10 (- 3.20 [- 4.21, - 2.20]). This systematic review and meta-analysis demonstrate significant alterations in inflammatory marker concentrations in blood samples of individuals with Alzheimer's disease and mild cognitive impairment. Elevated levels of IL-1β, IL-6, MCP-1, and TNF-α, alongside reduced IL-8 and IL-10 levels, suggest a robust inflammatory response associated with Alzheimer's disease.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"53"},"PeriodicalIF":3.9,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708318","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":"Ca²⁺-Affinitive and Non-Ca²⁺-Affinitive Synaptotagmins in Human Pan-cancer.","authors":"Xuanang Wu, Bo Gao, Kun Xiao, Nimra Saleem","doi":"10.1007/s12017-025-08873-x","DOIUrl":"10.1007/s12017-025-08873-x","url":null,"abstract":"<p><p>Synaptotagmins (Syts) are a family of crucial Ca²⁺ sensors for cellular secretions, while half of the Syt isoforms are evolutionarily non-Ca²⁺-affinitive, which are less studied but associated with several neuro-system diseases. Some Syt isoforms exhibited importance in specific cancer types, but a comprehensive study of all Syts in pan-cancer is lacking. Here, using informatics tools and proteome/transcriptome databases, the expression, phosphorylation, CpG methylation profiles, and the correlation with genome heterogeneity, tumor stemness, and immune infiltration of all human Syts are analyzed in human pan-cancer, resulting in significant associations of each Syt in various types of cancer, including pathological stage and prognosis. Most Syts exhibit noteworthy expression level changes in GBM/LGG and PCPG, and Syt11 has a strong association with immune infiltration. The Ca²⁺-affinitive and non-Ca²⁺-affinitive Syt groups show opposite changes in both expression and methylation levels in an overview scale suggesting different mechanisms of them in cancers. Detection of similar expression genes suggests that Ca²⁺-affinitive Syts may participate in the RNA-splicing process, while non-Ca²⁺-affinitive Syts are involved in NF-κB signaling and immune regulation. This study uncovers the clinical potential of each Syt isoform and discusses clues to their roles, such as Ca²⁺ sensitivity and immune regulation, in tumor progression. The overall data are informative for future refining and mining.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"52"},"PeriodicalIF":3.9,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659725","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":"Equol as a Multitarget Agent Against Neurodegeneration: Mechanistic Insights into Its Molecular Modulation.","authors":"Nushrat Jahan, Lovedeep Singh, Jyoti Sharma","doi":"10.1007/s12017-025-08875-9","DOIUrl":"10.1007/s12017-025-08875-9","url":null,"abstract":"<p><p>Neurodegenerative diseases consist of a group of progressive disorders characterized by the gradual decline in the structure or function of neurons, which ultimately results in neuronal death. The occurrence and societal effects of these disorders have been consistently rising, presenting considerable public health challenges globally. Multiple interconnected pathways, including oxidative stress, neuroinflammation, nitrosative stress, and apoptosis, drive their progression. NOX-induced ROS disrupts neuronal function, impairs mitochondrial activity, and triggers lipid peroxidation, contributing to neuronal death. Activation of the TLR-4/MAPK/NF-κB pathway triggers neuroinflammation and NLRP3 inflammasome activation. This inflammasome-driven inflammation accelerates neuronal injury and death. Moreover, reduced estrogen receptor expression weakens neuronal defenses, impairing synaptic function, thereby worsening neurodegeneration. Neurodegenerative diseases continue to be without a cure, as existing treatments focus on alleviating symptoms and modifying the disease. Due to their intricate and multifactorial pathophysiology, there is a pressing need for agents capable of targeting multiple pathological mechanisms to effectively combat these disorders. Various phytomolecules have shown promise in tackling different neurodegenerative diseases by modulating key molecular targets. Equol (4',7-isoflavandiol) is a metabolite of daidzein, a soy isoflavone present in soybeans and various other plant sources. Equol has shown significant promise in combating neurodegeneration by modulating mediators involved in oxidative stress, neuroinflammation, nitrosative stress, and apoptosis. Key signaling molecules influenced by equol include TLR-4, MAPKs, NLRP3 inflammasome, ROS, and inflammatory mediators, among others. Considering equol's ability to modulate these signaling mediators, this review explores the mechanistic pathways through which equol confers neuroprotection.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"51"},"PeriodicalIF":3.9,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642968","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":"Dysbiosis and Neurodegeneration in ALS: Unraveling the Gut-Brain Axis.","authors":"Vivek Kumar Sharma","doi":"10.1007/s12017-025-08870-0","DOIUrl":"10.1007/s12017-025-08870-0","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder marked by the progressive degeneration of motor neurons in the brain and spinal cord. Despite decades of research, ALS remains incurable, diagnostically elusive, and is accompanied by rapid clinical decline, morbidity, and mortality. Its pathophysiology involves a complex interplay of genetic mutations (SOD1, C9/f72), environmental triggers, oxidative stress, neuroinflammation, and the accumulation of misfolded proteins, such as TDP-43 and SOD1. These factors disrupt cellular homeostasis aggravates excitotoxicity and neuronal death. Existing treatments, such as riluzole (a glutamate release modulator) and edaravone (a free radical scavenger), offer limited benefits, modestly prolonging survival or slowing functional decline without halting progression. Investigational approaches include antisense oligonucleotides targeting mutant SOD1 or C9orf72 genes, stem cell-based motor neuron replacement, and biomarker discovery to enable earlier diagnosis and progression monitoring. ALS patients frequently exhibit gastrointestinal (GI) symptoms, including dysphagia, sialorrhea, constipation, delayed gastric emptying, and pancreatic/parotid deficiencies. These observations underscore a close association between GI dysfunction and ALS pathogenesis. Also, recent studies implicate the gut-brain-microbiota axis in disease evolution, with microbial metabolites influencing neuroimmune interactions, synaptic plasticity, myelination, and skeletal muscle function. These studies indicate that dysbiosis-an imbalance in gut microbiota-may have a crucial role in ALS progression by impairing intestinal barrier integrity, promoting endotoxemia, and driving systemic inflammation. Conversely, ALS progression itself worsens dysbiosis, creating a vicious cycle of neuroinflammation and neurodegeneration. Preclinical and clinical evidence suggests that interventions targeting gut microbiota-such as prebiotics, probiotics, antibiotics, or phage therapy-could alleviate symptoms and slow disease progression and specific probiotic strains have also shown promise in reducing oxidative stress and inflammation in animal models. These findings highlight the urgent need to elucidate the functional role of gut microbiota in ALS to unlock novel diagnostic and therapeutic avenues. This review synthesizes current knowledge on the pathophysiology of ALS, with a focus on the emerging role of the gut-brain-microbiota axis. It highlights how dysbiosis influences diverse disease markers and neurodegenerative mechanisms, offering insights into potential therapeutic strategies and identifying key research gaps and future directions.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"27 1","pages":"50"},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144554038","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}