Journal of Molecular Neuroscience最新文献

{"title":"Preclinical Evidence of Extracellular Vesicle-derived MicroRNAs in Relieving Diabetic Peripheral Neuropathy: A Systematic Review","authors":"Amir Reza Ghafourian,&nbsp;Atefeh Soltan Mohseni,&nbsp;Reyhaneh Ghasemi,&nbsp;Maryam Davoudi,&nbsp;Hamid Choobineh,&nbsp;Sheila Jafari,&nbsp;Fariba Nabatchian,&nbsp;Reza Afrisham","doi":"10.1007/s12031-026-02500-5","DOIUrl":"10.1007/s12031-026-02500-5","url":null,"abstract":"<div><p>Diabetic peripheral neuropathy (DPN) provokes axonal degeneration and impairs nerve repair. Preclinical studies suggest that extracellular vesicles (EVs) exert neuroregenerative effects. As miRNAs are key, transferable bioactive cargoes that mediate the majority of observed EV functions in cell-to-cell communication, this systematic review specifically evaluated animal model evidence on the therapeutic potential of EV-derived miRNAs in alleviating DPN. A comprehensive search of MEDLINE, Embase, and ISI Web of Science was conducted on March 21, 2025 following PRISMA 2020 (PROSPERO registration ID: CRD420251130044). This review included studies that utilized in vivo models of DPN and in vitro hyperglycemic models only when corroborated by in vivo validation within the same study. Functional, electrophysiological, and histological assessments of nerve regeneration constituted the outcomes. Data were qualitatively synthesized and their quality was assessed using SYRCLE’s Risk of Bias Tool. Nine studies met the inclusion criteria. The synthesis revealed a bidirectional regulatory role for EV miRNAs in DPN pathophysiology, dependent on both the miRNA species and the pathophysiological state of the EV source cell. Neuroprotective miRNAs (e.g., <i>miR-21</i>,<i> -146a</i>,<i> let-7a</i>,<i> -20b-3p</i>) from healthy or stem cell sources enhanced myelin integrity, nerve conduction, and neurovascularization, while mitigating neuroinflammation. Conversely, pathological hyperglycemia could reprogram EV cargo, leading to the enrichment of neurodegenerative miRNAs (e.g., <i>miR-28</i>,<i> -31a</i>,<i> -221</i>) that exacerbated neuropathic features. EV miRNAs exhibit significant improvement in peripheral nerve function, alleviating neuropathic pain, or promoting nerve regeneration under hyperglycemia. Nevertheless, preclinical research with more homogenous methods is necessary to advance clinical translation.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829502","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":"Viral Mimicry of Alzheimer’s Disease: Innate Sensing of Self-Nucleic Acids as a Driver of Glial Senescence","authors":"Qamar Abuhassan,&nbsp;Tamara Nazar Saeed,&nbsp;Ali Fawzi Al-Hussainy,&nbsp;R. Roopashree,&nbsp;Swati Mishra,&nbsp;Anima Nanda,&nbsp;Gunjan Mukherjee,&nbsp;Jasur Rizaev,&nbsp;Sada Ghalib Taher,&nbsp;Mariem Alwan,&nbsp;Mahmood Jawad,&nbsp;Hiba Mushtaq","doi":"10.1007/s12031-026-02532-x","DOIUrl":"10.1007/s12031-026-02532-x","url":null,"abstract":"&lt;div&gt;&lt;p&gt;Alzheimer’s disease (AD) is a devastating neurodegenerative disorder defined by progressive memory loss and synaptic failure. For decades, therapeutic development has focused on clearing amyloid-beta plaques, yet the repeated clinical failures of this approach necessitate a fundamental paradigm shift toward the brain’s immunometabolic landscape. The “Viral Mimicry” hypothesis posits that AD represents a state of sterile autoimmunity where the innate immune system mistakenly identifies self-nucleic acids as viral pathogens. This “ghost war” is ignited by the convergence of metabolic dysfunction and genomic instability: specifically, the leakage of mitochondrial DNA into the cytosol and the epigenetic derepression of ancient retrotransposons (LINE-1, HERVs). These endogenous ligands activate the cGAS-STING cytosolic sensing axis, a pathway that drives a chronic interferon response. Consequently, microglia and astrocytes are transformed into senescent, pro-inflammatory phenotypes that release a toxic Senescence-Associated Secretory Phenotype (SASP), directly fueling synaptic elimination. Crucially, major genetic risk factors, including APOE4 and TREM2 variants, exacerbate this cascade by compromising mitochondrial integrity and lipid metabolism, thereby sensitizing the brain to innate surveillance failure. By reconceptualizing AD as an acquired interferopathy driven by the “enemy within,” this framework highlights novel therapeutic targets. Specifically, repurposing Nucleoside Reverse Transcriptase Inhibitors (NRTIs) to block retrotransposition and deploying senolytics to clear dysfunctional glia offer promising strategies to arrest the progression from healthy aging to cognitive decline. This review synthesizes current research on the molecular mechanisms of viral mimicry, detailing the impact of genetic risk factors and evaluating emerging therapeutic interventions targeting this innate immune axis.&lt;/p&gt;&lt;h3&gt;Graphical Abstract&lt;/h3&gt;&lt;div&gt;&lt;figure&gt;&lt;div&gt;&lt;div&gt;&lt;picture&gt;&lt;source&gt;&lt;img&gt;&lt;/source&gt;&lt;/picture&gt;&lt;span&gt;The alternative text for this image may have been generated using AI.&lt;/span&gt;&lt;/div&gt;&lt;div&gt;&lt;p&gt;The Shift from Molecular Containment to Viral Mimicry in Alzheimer’s Disease. The figure contrasts the physiological state of healthy aging with the pathological state of Alzheimer’s Disease. (Left) In the healthy brain, \"Molecular Containment\" is maintained: immunogenic mitochondrial DNA is sequestered within the organelle, and ancient retrotransposons are epigenetically silenced within the nucleus. (Right) In Alzheimer’s Disease, the convergence of genomic instability and metabolic failure leads to a \"loss of inhibition\". The derepression of retroelements (LINE-1 (long interspersed nuclear element-1) dsDNA, HERV dsRNA) and the leakage of mitochondrial DNA into the cytosol activate the cGAS-STING innate immune axis. This viral mimicry transforms microglia into a senescent, Lipid-Droplet Accumulating phenotype, driving a chronic Type I Interferon response th","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809205","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":"Beyond Amyloids: Neuroprotective Potential of Betanin and its Derivatives Against Alpha-Synuclein Aggregates and ROS Overload in Parkinson’s Disease","authors":"Ayda Ghahari,&nbsp;Alireza Alikhanian,&nbsp;Fatemeh Akhond Solaei,&nbsp;Arghavan Fattahi,&nbsp;Hamdam Hourfar,&nbsp;Anett Schallmey,&nbsp;Mehdi Mohammadi,&nbsp;Dina Morshedi","doi":"10.1007/s12031-026-02534-9","DOIUrl":"10.1007/s12031-026-02534-9","url":null,"abstract":"<div><p>The aggregation of alpha-synuclein (αSN) is a key pathological feature of Parkinson’s disease (PD), leading to neural cell death via reactive oxygen species (ROS) overload and activation of downstream neurotoxic pathways. Betanin, a beetroot-derived small molecule, has exhibited antioxidant and neuroprotective properties. In this study, three betaxanthins—Bxn-A, Bxn-B, and Bxn-C—were chemically synthesized from betanin to enhance its therapeutic properties. Betaxanthin Bxn-A effectively reduced intracellular ROS levels without cytotoxicity, even at 500 µM. Additionally, betanin and its derivatives revealed neuroprotective effects, including significant reductions in apoptosis, preservation of mitochondrial membrane potential, modulated autophagy, and enhanced cell viability in PD-model cells. In terms of aggregation inhibition, betaxanthins Bxn-A and Bxn-B significantly reduced αSN aggregation compared to the control after 48 h of incubation. Betaxanthin Bxn-A also triggered disaggregation of existing aggregates and inhibited formation of large, insoluble species. Moreover, αSN aggregation and disaggregation products formed in the presence of betanin or its derivatives exhibited significantly lower cytotoxicity than those formed in their absence. Specifically, cells treated with aggregates formed in the presence of 50 µM betaxanthin Bxn-B showed 100% viability, while those treated with disaggregation products formed in the presence of 100 µM betaxanthin Bxn-A showed 20% greater viability than those treated with untreated disaggregates. Molecular docking revealed interactions between betaxanthins and key αSN residues, suggesting destabilization mechanisms. Docking analyses with five ROS-PPI network key proteins—C5, CDC42, BCL2, CDKN1A, and CDKN1B—indicated potential roles in inhibiting oxidative stress-related pathways. Drug-likeness predictions indicated that the derivatives enhanced pharmacological potential, making them promising candidates for PD treatment.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809170","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":"Identification of Mitochondrial Dysfunction Genes as Diagnostic Biomarkers for Ischemic Stroke by Integrated Bioinformatics Analysis and Machine Learning","authors":"Dandan Wu,&nbsp;Xiaolan Huang,&nbsp;Jie Li,&nbsp;Dingmin Mo,&nbsp;Weiwei Lan,&nbsp;Zihan Song,&nbsp;Li Su,&nbsp;Jianxiong Long,&nbsp;Jialei Yang","doi":"10.1007/s12031-026-02533-w","DOIUrl":"10.1007/s12031-026-02533-w","url":null,"abstract":"<div><p> Current diagnostics for ischemic stroke (IS) lack timeliness and accessibility, highlighting the need for novel molecular diagnostic models. Three gene expression datasets (GSE16561, GSE22255 and GSE58294), encompassing both IS patients and healthy control subjects, were retrieved from a public database. The mitochondrial dysfunction genes retrieve from the intersection of the GeneCards and MitoCarta3.0 databases. The limma and WGCNA package were used to obtain the genes related to IS. Feature genes were screened using LASSO, RF, SVM, and diagnostic models were constructed using NeighborMethod, NeuralNet, and BayesMethod. 3548 differentially expressed genes (DEGs) (1538 upregulated, 2010 downregulated) were identified in IS patients when compared to controls. WGCNA analysis yielded 10 IS-related modules containing 1643 genes. The intersection of DEGs, module genes, and mitochondrial dysfunction genes yielded 100 mitochondrial dysfunction genes associated with IS. These genes collectively regulate biological processes like mitochondrial ATP synthesis coupled electron transport and respiratory electron transport chain, and participate in IS-associated signaling pathways such as reactive oxygen species and oxidative phosphorylation. Further machine learning methods identified 4 feature genes, including <i>MCL1</i>, <i>MRPL46</i>, <i>MTX3</i> and <i>RNASEH1</i>. These four genes exhibited robust diagnostic potential in the merged dataset (all AUC &gt; 0.7). The machine learning models achieved AUC values of 0.814 (NeighborMethod), 0.852 (NeuralNet), and 0.842 (BayesMethod). External validation using an independent cohort confirmed that all models maintained high diagnostic accuracy (AUC range: 0.730–0.783). This study established a multi-gene diagnostic model for IS, identifying novel molecular biomarkers to improve the timeliness and accessibility of IS diagnosis.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809184","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":"Severe SPTBN4-Related Neurodevelopmental Disorder: Case Report of Two Siblings with Lethal Outcomes","authors":"Maram Abdalla,&nbsp;Lana Mashal,&nbsp;Werner Diehl,&nbsp;Amal Al Tenaiji,&nbsp;Afsheen Raza,&nbsp;Laura M. Winter-Paquette","doi":"10.1007/s12031-026-02498-w","DOIUrl":"10.1007/s12031-026-02498-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Spectrin beta non-erythrocytic 4 (SPTBN4) disorder is a rare yet impactful condition that is also known as neurodevelopmental disorder with hypotonia, neuropathy, and deafness (NEDHND). It is caused by homozygous or compound heterozygous mutations in the <i>SPTBN4</i> gene, which encodes beta IV (βIV) spectrin primarily found in neurons and pancreatic islets. Here, we report two male siblings from a Syrian non-consanguineous (possibly distantly related) family diagnosed with SPTBN4 disorder. Both patients exhibited severe failure to thrive, hypotonia, dysphagia, and global developmental delay, initially suggesting spinal muscular atrophy (SMA). Further testing has ruled out SMA for both patients, and the older sibling died undiagnosed at the age of 1 year and 6 months. Subsequently, whole genome sequencing (WGS) revealed a novel homozygous nonsense c.508 A &gt; T p. (Lys170*) variant in the <i>SPTBN4</i> gene in the younger sibling, and he died at the age of 2 years and 7 months with a presumed diagnosis of NEDHND. Upon the confirmation of the mutation in DNA stored from the older sibling, the variant was reclassified from a variant of uncertain significance (VUS) to likely pathogenic, enabling prenatal genetics testing for future pregnancies. This case study reports a novel lethal genetic variant in the <i>SPTBN4</i> gene in two siblings, capturing their clinical progression, and comparing them with recent cases to highlight both common and unique features associated with NEDHND. The report’s findings provide valuable insights into the UAE cohort, contributing to the limited body of knowledge on variants present in Arab populations.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796393","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":"Differential Involvement of t-SNARE Proteins and Signaling Pathways During PGE2-Induced TRPV1 Sensitization","authors":"Sahar M. Jaffal,&nbsp;Samer Alqaralleh,&nbsp;Munther S. Alnajjar","doi":"10.1007/s12031-026-02529-6","DOIUrl":"10.1007/s12031-026-02529-6","url":null,"abstract":"<div><p>Prostaglandin E2 (PGE2) is a significant mediator of inflammatory pain that causes sensitization of the transient receptor potential vanilloid 1 (TRPV1) channels in primary sensory neurons. Previous research focused on intracellular signaling pathways; however, the role of vesicular trafficking mechanisms in TRPV1 sensitization is not fully elucidated. In this study, we examined whether PGE2-induced TRPV1 sensitization correlates with distinct regulation of t-SNARE proteins in dorsal root ganglia (DRG) and peripheral tissues, utilizing a rat model of inflammatory pain. We used behavioral tests, different inhibitors, DRG neuronal cultures, and protein expression tests. We observed that PGE2-induced sensitization correlates with a reduction in SNAP25 expression in DRG neurons and a decrease in syntaxin-1 expression in peripheral tissues. Pharmacological inhibition of various signaling pathways diminished PGE2-induced hyperalgesia in hyperalgesic priming model and modified t-SNARE protein expression. These results suggest, rather than definitively establish, the involvement of the following signaling pathways in capsaicin-induced mechanical allodynia: PKCε, cAMP, PLC, SNAP25, p38 MAPK, JNK MAPK, ERK-MAPK, PKC, PKA, CaMKII, CDK5, intracellular and extracellular Ca²⁺. The differential regulation of t-SNARE proteins may be linked to TRPV1 sensitization in a tissue-specific manner. Nonetheless, since only total protein levels were evaluated and no direct measurements of membrane trafficking were conducted, additional studies are necessary to elucidate the mechanistic role of t-SNARE proteins in TRPV1 surface localization and function.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147796897","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":"Expanding the Clinical Spectrum of LYRM7-Associated Mitochondrial Complex III Deficiency: Insights from New Cases and Literature Review","authors":"Golazin Shahbodagh Khan,&nbsp;Shiva Bayat,&nbsp;Reza Azizimalamiri,&nbsp;Mohammad Nikoohemmat,&nbsp;Narges Mashayekhi,&nbsp;Sahar Nabilou,&nbsp;Ali Reza Tavasoli,&nbsp;Mahmoud Reza Ashrafi,&nbsp;Morteza Heidari","doi":"10.1007/s12031-026-02527-8","DOIUrl":"10.1007/s12031-026-02527-8","url":null,"abstract":"<div><p>Mitochondrial complex III (CIII) deficiency, resulting from abnormalities in its subunits or assembly factors, presents with diverse clinical manifestations. LYRM7-associated CIII deficiency is rare and typically presents with progressive neurodegeneration. We report a case series of <i>LYRM7</i>-associated CIII deficiency in two brothers, highlighting inflammatory demyelinating-like presentations, intrafamilial variability, and atypical disease progression. We present an investigational case series highlighting continuing challenges in diagnosing and managing <i>LYRM7</i>-associated mitochondrial complex III deficiency. Whole-exome sequencing (WES) was performed for diagnostic evaluation, followed by confirmatory Sanger sequencing and literature review of previously reported cases. Two brothers from a consanguineous family presented with ataxia, visual impairment, and progressive neurological deterioration including spasticity, seizures, cognitive decline, and motor weakness. Patient 1 (P1) experienced recurrent ataxic episodes beginning at 7 years of age, initially suspected to represent an inflammatory demyelinating disorder, while patient 2 (P2) demonstrated a more aggressive disease course with rapid neurological deterioration and early mortality at 8 years of age. Neuroimaging revealed cystic white matter changes suggestive of mitochondrial leukodystrophy and longitudinally extensive transverse myelitis (LETM) in both patients, differing from typical inflammatory demyelinating patterns. Genetic testing confirmed a pathogenic <i>LYRM7</i> variant. Notably, intrafamilial clinical variability and the inflammatory-like presentation in P1- including LETM and optic neuritis mimicking neuromyelitis optica spectrum disorder (NMOSD)- distinguished our cases from previously reported patients. These findings expand the phenotypic spectrum of <i>LYRM7</i>-associated CIII deficiency and highlight diagnostic challenges. This case series expand the clinical spectrum of <i>LYRM7</i>-associated complex III deficiency and highlights relapsing inflammatory-like presentations as a potential diagnostic pitfall. Our findings emphasize the importance of considering mitochondrial disorders in children presenting with recurrent demyelinating-like episodes, atypical progression, or familial patterns. Early genetic diagnosis is essential for accurate diagnosis, counseling, and management of mitochondrial disorders. </p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759188","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":"Neuroprotective Effects of Semaglutide in Cyclophosphamide-Induced Neuropathy: Restoring SIRT1/AMPK, PI3K/AKT/mTOR, and Antioxidant Pathways","authors":"Hossein M. Elbadawy,&nbsp;Mohannad A. Almikhlafi,&nbsp;Tahani Saeedi,&nbsp;Mohammed H. Alsubhi,&nbsp;Abdulrahman A. Aljabri,&nbsp;Yosra Assem Hussien,&nbsp;Mevidette Elmadani,&nbsp;Hany M. Fayed,&nbsp;Rehab F. Abdel-Rahman","doi":"10.1007/s12031-026-02521-0","DOIUrl":"10.1007/s12031-026-02521-0","url":null,"abstract":"<div>\u0000 \u0000 <p>Cyclophosphamide (CP), a widely used chemotherapeutic agent, often induces chemotherapy‑induced peripheral neuropathy (CIPN). CP metabolism generates acrolein, a reactive aldehyde that promotes oxidative stress, lipid peroxidation, mitochondrial dysfunction, and NF‑κB–mediated neuroinflammation, while impairing PI3K/AKT/mTOR signaling. These processes drive axonal degeneration, demyelination, and neuronal apoptosis, highlighting the need for novel therapies. This study examined the neuroprotective effects of semaglutide, a glucagon‑like peptide‑1 (GLP‑1) receptor agonist, in a rat model of CP‑induced neuropathy. Wistar rats were assigned to control, CP (200 mg/kg, IP), or CP plus semaglutide (12–40 µg/kg, SC every three days). Motor and sensory functions were assessed using rotarod, hot plate, tail flick, and cold allodynia tests. Sciatic nerves were analyzed for oxidative stress markers (GSH, SOD, MDA), inflammatory cytokines (TNF‑α, IL‑6), apoptotic regulators (Caspase‑3, BAX, Bcl‑2), and signaling proteins (SIRT1, AMPK, PI3K, AKT, mTOR). Histopathology and immunohistochemistry evaluated structural integrity and Nrf2/p‑AKT expression. CP caused marked motor incoordination (‑31.3% rotarod latency) and sensory hypersensitivity (thermal: ‑60.7%; cold: ‑46.6%; tail flick: ‑31.4%). Semaglutide dose‑dependently reversed these deficits, with the higher dose restoring near‑normal function. Mechanistically, semaglutide reduced oxidative stress, upregulated SIRT1 and AMPK, suppressed TNF‑α and IL‑6, rebalanced apoptotic markers, and restored PI3K/AKT/mTOR signaling. Histology confirmed protection against edema and demyelination, while immunohistochemistry showed recovery of Nrf2 and p‑AKT. Overall, semaglutide provides multimodal neuroprotection against CP‑induced neuropathy, supporting its potential as a therapeutic candidate for CIPN.</p>\u0000 </div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759172","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":"Nicotinamide Riboside (NR) Supplementation Exerts Neuroprotective Effects in db/db Mouse Model of Type 2 Diabetes","authors":"Eleni Hughes,&nbsp;Keely Barton,&nbsp;Daliya Rizvi,&nbsp;Katelyn Dial,&nbsp;Xiaoxin X. Wang,&nbsp;Komuraiah Myakala,&nbsp;Brent T. Harris,&nbsp;G. William Rebeck,&nbsp;Moshe Levi","doi":"10.1007/s12031-026-02499-9","DOIUrl":"10.1007/s12031-026-02499-9","url":null,"abstract":"<div><p>Type 2 diabetes is linked to neuropsychiatric complications such as anxiety-like behaviors, disrupted brain metabolism, neuroinflammation, and impaired mitochondrial function. Nicotinamide riboside (NR) has emerged as a potential therapeutic agent for these complications due to its role in NAD + biosynthesis and neuroprotective properties. In this study, we assessed whether NR supplementation can ameliorate anxiety-like behavior in a mouse model of type 2 diabetes by modulating the hippocampal inflammatory response. 8-week-old db/db mice on the BKS background were used as a model of type 2 diabetes, and db/m mice were used as non-diabetic controls. Four groups, consisting of non-diabetic and diabetic mice, were fed with a control diet or a diet supplemented with NR at 500 mg/kg dosage for 20 weeks. The open field test and nesting behavioral assessments were conducted to evaluate anxiety-related behaviors and overall well-being. After animals were euthanized, biochemical analyses were performed on hippocampal samples using RT-qPCR, Western blotting, and immunohistochemistry. Behavioral assessments revealed increased anxiety and reduced nest-building motivation in db/db mice compared with control mice. These effects were ameliorated by NR treatment. Biochemical analyses revealed that NR attenuated markers of inflammation, including astrocytosis and microglial activation, activation of inflammatory signaling via STING and NF-kB, and pro-inflammatory cytokines. Our findings show that NR supplementation reduces anxiety-like symptoms and neuroinflammation in diabetic mice, highlighting the potential therapeutic relevance of NR in mitigating neuropsychiatric complications associated with diabetes mellitus.</p></div>","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759210","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":"Correction: Cutaneous α-Synuclein Pathology as a Differential Marker: A Histological and Statistical Comparison across Neurodegenerative Disease Groups","authors":"Dorota Šebelová,&nbsp;Kateřina Menšíková,&nbsp;Michaela Kaiserová,&nbsp;Lenka Satke,&nbsp;Zuzana Grambalová,&nbsp;Kateřina Čížková,&nbsp;Zdeněk Tauber,&nbsp;Kateřina Klíčová,&nbsp;Dominik Hraboš,&nbsp;Sarah E. V. Cook,&nbsp;Jana Zapletalová,&nbsp;Petr Kaňovský","doi":"10.1007/s12031-026-02515-y","DOIUrl":"10.1007/s12031-026-02515-y","url":null,"abstract":"","PeriodicalId":652,"journal":{"name":"Journal of Molecular Neuroscience","volume":"76 2","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759137","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}