NeuroMolecular Medicine最新文献

{"title":"Transcription Factor SPI1 Mediates Chronic Neuropathic Pain by Activating NLRC4 Transcription to Drive Microglial Activation and Inflammation.","authors":"Liyuan Qin, Qiang Fu, Xiaoling Wang, Quanbo Li","doi":"10.1007/s12017-026-08913-0","DOIUrl":"https://doi.org/10.1007/s12017-026-08913-0","url":null,"abstract":"<p><p>Microglial polarization plays a key role in the process of chronic neuropathic pain (CNP). This study aims to investigate the molecular mechanism by which the transcription factor SPI1 mediates microglial polarization and participates in CNP by regulating NOD-like receptor C4 (NLRC4) expression. The GSE124272 dataset (blood samples of 8 intervertebral disc degeneration patients and 8 controls) was obtained from the GEO database, and the differentially expressed genes (DEGs) were screened. The intersection of DEGs with neuropathic pain related genes in GeneCards was taken. Support vector machine-recursive feature elimination algorithm was used to identify hub genes. Human microglia (HMC3) were stimulated with lipopolysaccharides (LPS) to construct an inflammation model. qRT-PCR, western blot, ELISA, flow cytometry, and reactive oxygen species (ROS) detection were used to evaluate gene expression, inflammatory factor levels, cell polarization, and ROS levels. ChIP and dual-luciferase reporter assay were used to verify the binding of SPI1 to NLRC4 promoter and its transcriptional regulation. A rat model of chronic constriction injury (CCI) was established to evaluate the effect of shNLRC4 on CNP in vivo. After screening and machine learning, NLRC4 was one of the five hub genes, and its expression was significantly upregulated in LPS-induced HMC3 cells. NLRC4 knockdown inhibited LPS-induced M1 polarization, the release of pro-inflammatory factors, ROS production, and the expression of microglia activation marker Iba1, while promoted the expression of M2 polarization markers. SPI1 could directly bind to the NLRC4 promoter to increase its transcription. Overexpression of NLRC4 reversed the inhibitory effect of SPI1 knockdown on LPS-induced microglial activation and inflammation. In CCI rat model, knocking down NLRC4 significantly alleviated mechanical and thermal hyperalgesia, and reduced the levels of NLRC4 and inflammatory factors (TNF-α, IL-1β, and IL-6) in the spinal cord tissues. SPI1 acts as a transcription factor to directly increase NLRC4 transcription, thereby promoting microglial activation and neuroinflammatoion, and ultimately accelerating the development of CNP.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840685","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":"Enhanced Neurophysiological Benefits of Magnesium-Acetyl-Taurate Over Magnesium-L-Threonate: A Comparative pre-clinical Study on Bioavailability, Synaptic Plasticity and Cognitive Functions.","authors":"Aakash Kumar, Sidharth Mehan, Sumedha Gupta, Ghanshyam Das Gupta, Rajaram Samant, Manoj Tongra","doi":"10.1007/s12017-026-08929-6","DOIUrl":"https://doi.org/10.1007/s12017-026-08929-6","url":null,"abstract":"&lt;p&gt;&lt;p&gt;The study examines how magnesium compounds, especially Magnesium-L-Threonate (MLT) and Magnesium-Acetyl-Taurate (MAT), affect neurophysiological functions in adult Wistar rats. Magnesium is essential for many cellular processes in the brain & peripheral system, such as neurotransmitter regulation, muscle function, and energy metabolism. Tissue Mg²⁺ levels were defined as the primary endpoint of the study, as they directly reflect the central objective of evaluating magnesium-based interventions. All other outcomes, including behavioral, biochemical, and molecular parameters, were considered secondary endpoints. This research aimed to compare the brain effectiveness of MLT (115 mg/kg and 450 mg/kg) and MAT (150 mg/kg and 500 mg/kg) in raising magnesium levels in biological samples like blood plasma, cerebrospinal fluid (CSF), muscles and brain tissues. The aim is to examine the effect of Magnesium compounds (MLT, MAT & combination treatment) on modulation and alterations in all the biological markers for neuroinflammation, synaptic plasticity, neurotransmission balance, oxidative stress & mitochondrial functioning. MAT showed better Mg&lt;sup&gt;2+&lt;/sup&gt;, resulting in more notable improvements in cognitive functions, neuromuscular strength, and motor coordination compared to MLT. Behavioral tests indicated that MAT and the combined therapy of MLT and MAT significantly improved spatial learning, memory, and anxiety-related behaviors. These improvements correlated with increased expression of key proteins, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), Nrf2, HO-1, cAMP, and synaptic proteins such as synaptophysin and PSD-95, which are crucial for synaptic plasticity and cognition. Additionally, MAT treatment was associated with alteration inantioxidant markers, including superoxide dismutase (SOD), glutathione (GSH), catalase, and coenzyme Q10 (CoQ10), indicating better cellular defense against oxidative stress. Moreover, the upregulation of Mitochondrial ETC complexes by MAT and the combination therapy of MLT and MAT suggest improved mitochondrial function inside cells. Levels of Threonate, Taurine, and Mg&lt;sup&gt;2+&lt;/sup&gt; were also significantly higher in the MAT, MLT, and combined treatment groups. Neurotransmitters such as Dopamine, GABA & Glutamate, as well as complete blood count, have also been estimated. Morphological and histological analyses showed that MAT and the combination therapy significantly enhanced neuronal myelination and structural integrity across various brain regions. These results suggest that MAT & MLT + MAT could serve as a promising neurotherapeutic agent due to its ability to improve better magnesium bioavailability, stimulate neurogenesis, enhance cognitive functions & overall brain functioning. Future research should focus on refining methods for higher-brain bioavailable magnesium salt supplementation and investigating the combined effects of such magnesium salts with oth","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840719","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":"Revisiting the Peripheral Nerve Injury and Regeneration.","authors":"Zhen-Gang Liu, Yun-Long Zou, Min-Xin Zhang, Fan Yang, Peng-Fu Li, Bo-Yin Zhang","doi":"10.1007/s12017-026-08914-z","DOIUrl":"https://doi.org/10.1007/s12017-026-08914-z","url":null,"abstract":"<p><p>Peripheral nerve injury significantly impacts patients' quality of life, with poor nerve regeneration and insufficient functional recovery being urgent challenges. Even with early medical and surgical interventions, desired outcomes are often not achieved. Our research focuses on effective surgical and rehabilitation strategies, as well as the development of innovative technologies. Peripheral nerve injury repair is analyzed from three main perspectives: first, improving intrinsic axonal growth capacity, which involves signaling pathways and the regulation of neuromodulatory factors; second, enhancing the injury repair environment, where Schwann cells (SCs) and macrophages play key roles in reducing inhibitory factors, and regulating the immune microenvironment is crucial; and third, ensuring the successful and correct reconnection of the repaired nerve to the innervated tissue, preventing distal tissue degeneration and scar formation. This review explores concepts related to peripheral nerve injury (PNI) and the associated anatomical changes, offering a schematic representation of the various types of nerve damage. We review studies conducted in experimental models of peripheral nerve injury treatment, discussing existing treatment methods-such as surgical interventions, drug-based therapies, and other approaches-and highlight new PNI treatments, particularly for critical lesions, aimed at overcoming existing limitations and achieving better clinical outcomes.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777282","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":"Sortilin is Associated with PGRN-Mediated Endoplasmic Reticulum Stress and Activation of Microglia in a Rat Model of Degenerative Cervical Myelopathy.","authors":"Linkai Lei, Xinping Wang, Jianfeng Zhang, Jijuan Zhao","doi":"10.1007/s12017-026-08927-8","DOIUrl":"https://doi.org/10.1007/s12017-026-08927-8","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777442","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":"Exosomal miR-1278 From Bone Marrow Mesenchymal Stem Cells Modulates Ldha-Mediated Microglia Polarization to Decelerate Parkinson's Disease Pathology.","authors":"Wenci Yan, Shuainan Ma, Ruyue Liu, Chang Liu, Chunyan Wang","doi":"10.1007/s12017-026-08920-1","DOIUrl":"https://doi.org/10.1007/s12017-026-08920-1","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777332","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":"Naftidrofuryl Exerts Neuroprotective Effects in a Rotenone-Induced Rat Model of Parkinson's Disease Through Modulation of PINK1/Parkin and ER Stress Pathways.","authors":"Saad Misfer Alqahtani, Ehab A M El-Shoura, Lobna A Abdelzaher, Souty M Z Sharkawi, Ahmed M Atwa, Maha Hosni Morsi, Hebatallah M Saad, Basel A Abdel-Wahab","doi":"10.1007/s12017-026-08925-w","DOIUrl":"https://doi.org/10.1007/s12017-026-08925-w","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729585","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":"SIRT1 Activators as Geroprotective Agents in Brain Aging: Mechanisms and Therapeutic Potential.","authors":"Ayman Ali Mohammed Alameen, Hayder M Al-Kuraishy, Ali I Al-Gareeb, Athanasios Alexiou, Marios Papadakis, Safaa A Faheem, Gaber El-Saber Batiha","doi":"10.1007/s12017-026-08923-y","DOIUrl":"10.1007/s12017-026-08923-y","url":null,"abstract":"<p><p>The brain undergoes profound molecular and structural changes during the aging process, resulting in the development of neurodegeneration, cognitive impairment, and increased vulnerability to chronic diseases. At the cellular level, brain aging is characterized by oxidative damage, genomic instability, and chronic low-grade inflammation known as inflammaging. Central to this process is Sirtuin 1 (SIRT1), a NAD⁺-dependent class III histone deacetylase, known for its regulatory role in chromatin remodeling, oxidative stress responses, mitochondrial biogenesis, and neuroplasticity. Recent research has identified SIRT1 as a molecular target capable of reversing or attenuating several hallmarks of aging, particularly within the central nervous system (CNS). This narrative review critically evaluates the emerging evidence surrounding the geroprotective effects of SIRT1 activators, which exert dual actions, senomorphic and senolytic, via modulation of signaling pathways, thereby reducing neuronal senescence, enhancing autophagy, and mitigating inflammatory responses. The discussion also addresses the region-specific role of SIRT1 across the brain, particularly in the hippocampus and hypothalamus, which are essential for memory, energy homeostasis, and resilience to stress. Additionally, this review explores how SIRT1 depletion during aging contributes to the development of synaptic dysfunction, impaired cognitive function, and susceptibility to neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The therapeutic potential of SIRT1 activators is supported by preclinical and early clinical studies, suggesting their value in preventing or delaying brain aging. Thus, SIRT1 could be a promising pharmacological target for age-associated brain disorders, warranting more robust translational studies to validate these findings in humans.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618951","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":"Genistein mitigates estrogen deficiency and chronic stress-induced neuronal dysfunction via targeting ER-β, oxidative stress, inflammation, and apoptosis.","authors":"Bharti Bhardwaj, Rishabh Chaudhary, Sowvik Bag, Dhrubalochan Rana, Nidhi Gupta, Nitin Bansal, Seema Bansal","doi":"10.1007/s12017-026-08915-y","DOIUrl":"https://doi.org/10.1007/s12017-026-08915-y","url":null,"abstract":"<p><p>Both postmenopausal estrogen decline and chronic unpredictable mild stress (CUMS) contribute to the onset and progression of brain dysfunctions in women. Genistein, a phytoestrogen predominantly found in soy and soy products, may reverse brain dysfunctions. Therefore, the current study focused on determining the effect of GEN in the modulation of brain dysfunction by using the Ovariectomized (OVX)-CUMS rat model. To induce postmenopausal brain dysfunction, female SD rats were bilaterally OVX and then exposed to CUMS for a total of 28 days. Various basic physiological and neurobehavioral parameters were performed. Oxidative stress was measured in the brain. Brain inflammation (TNF-α, IL-6, & NF-kB/p65), apoptotic (Bax) and anti-apoptotic (Bcl-2) markers were analyzed using RT-PCR and/or ELISA. Decreased estrogen levels and CUMS both combinedly cause a reduction in serum estradiol levels, downregulation of ER-α and ER-β genes, and enhancement of oxidative stress, neuroinflammation, and apoptosis. Collectively, all these factors were responsible for the development of neuronal dysfunctions. GEN at doses of 10 & 20-mg/kg significantly and dose dependently restores serum estradiol levels and ER-β gene expression. With this, genistein also reduces oxidative stress, apoptosis, and neuroinflammation in the brain of OVX-CUMS rats. Thus, GEN (10 & 20-mg/kg) dose-dependently restores the estrogen deficiency and chronic stress-induced brain dysfunction.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468944","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":"Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) as a Biomarker of Neurodysfunction.","authors":"Victoria Linden de Rezende, Khiany Mathias, Lucineia Gainski Danielski, Tatiana Barichello, Fabricia Petronilho","doi":"10.1007/s12017-026-08912-1","DOIUrl":"10.1007/s12017-026-08912-1","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12982231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444421","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":"Lipocalin-2 in Intracerebral Hemorrhage: Mechanisms, Biomarker Potential, and Therapeutic Targeting.","authors":"Yue Sun, Wentao Sun, Lei Zheng, Baiwen Zhang, Jiawei Liu, Wei Zou","doi":"10.1007/s12017-026-08919-8","DOIUrl":"https://doi.org/10.1007/s12017-026-08919-8","url":null,"abstract":"","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":"28 1","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390721","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}