Journal of neuroimmunology最新文献

{"title":"Efficacy of FcRn antagonist efgartigimod in the treatment of Miller-Fisher/Guillain-Barré overlap syndrome: Two case reports.","authors":"Tingting Fan, Yan Jiang, Wei Hu, Wen Xu","doi":"10.1016/j.jneuroim.2025.578712","DOIUrl":"10.1016/j.jneuroim.2025.578712","url":null,"abstract":"<p><strong>Introduction: </strong>Guillain-Barré Syndrome (GBS) remains one of the most prevalent acute immune-mediated polyneuropathies. Miller Fisher Syndrome (MFS), a clinically distinct variant of GBS, is characterized by the classic triad of ataxia, areflexia, and ophthalmoplegia. The Miller-Fisher/Guillain-Barré (MFS/GBS) overlap syndrome represents an uncommon clinical entity with limited therapeutic options. Current management primarily relies on high-dose corticosteroid pulse therapy, intravenous immunoglobulin (IVIg), and plasma exchange; however, these interventions often demonstrate suboptimal clinical efficacy, particularly in resolving persistent ophthalmoplegia and bulbar symptoms. Efgartigimod, a humanized FcRn receptor antagonist, promotes lysosomal degradation of IgG antibodies, leading to rapid reduction of pathogenic autoantibodies. This mechanism positions efgartigimod as a promising treatment for antibody-mediated autoimmune disorders.</p><p><strong>Case presentation: </strong>We describe two cases of severe MFS/GBS overlap syndrome. Both patients had preceding infectious prodromes and presented with profound symptoms, including complete external ophthalmoplegia, truncal ataxia, areflexia, dysphagia, and limb paresthesia. Upon admission, standard therapy was initiated with IVIg (0.4 g/kg/day for 5 days) followed by methylprednisolone (0.5 g/day for 5 days). While minimal improvement in eye fixation was observed, dysphagia and limb numbness remained unchanged. Subsequently, both patients received two doses of efgartigimod (10 mg/kg) over two weeks. At 30-day post-discharge follow-up, both patients exhibited sustained improvement in ocular motility and regained independent ambulation.</p><p><strong>Conclusion: </strong>This report highlights two cases of treatment-refractory MFS/GBS overlap syndrome demonstrating suboptimal response to conventional immunomodulatory therapies. Efgartigimod emerges as a valuable treatment, offering clinical benefit in managing severe MFS/GBS overlap syndrome.</p>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"407 ","pages":"578712"},"PeriodicalIF":2.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804345","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":"A rare cause of visual impairment in patients with multiple sclerosis: Uveitis.","authors":"Mahmut Sami Biçimveren, Şerife Nur Çiftçi, Gülay Alp","doi":"10.1016/j.jneuroim.2025.578714","DOIUrl":"10.1016/j.jneuroim.2025.578714","url":null,"abstract":"<p><p>A patient with multiple sclerosis may experience motor, sensory, speech, and visual symptoms depending on the location of central nervous system demyelinating plaque involvement. The most common clinical presentation with visual symptoms is unilateral optic neuritis. However, uveitis rarely causes visual impairment in patients with multiple sclerosis. Multiple sclerosis-associated uveitis may occur after the diagnosis or years before the diagnosis of multiple sclerosis. We report a case of multiple sclerosis that was diagnosed 10 years after uveitis attacks. A 21-year-old female complained of numbness in her left half of the body for 3 days. Her medical history, it was noted that she had been treated for uveitis attacks and glaucoma and retinal detachment 10 years ago. Diagnostic studies for uveitis attacks did not reveal any etiology. Azathioprine and colchicine were recommended to prevent uveitis attacks and the patient was still taking these two medications regularly. Magnetic resonance imaging performed due to focal neurological symptoms showed images compatible with multiple sclerosis plaques. Oligoclonal band type 3 in the cerebrospinal fluid. She was evaluated by an ophthalmologist and a rheumatologist. No rheumatological cause was found. Ophthalmological evaluation was consistent with previous anterior and intermediate uveitis. Previous uveitis attacks were considered multiple sclerosis-associated uveitis. We recommended follow-up with interferon 1β treatment, which is effective in both multiple sclerosis and multiple sclerosis-associated uveitis.</p>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"407 ","pages":"578714"},"PeriodicalIF":2.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144804280","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":"Celia Fildes Brosnan (Jan. 5, 1938 - Feb. 10, 2025) Neuroimmunologist and Friend Extraordinaire.","authors":"Cedric S Raine","doi":"10.1016/j.jneuroim.2025.578702","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2025.578702","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"407 ","pages":"578702"},"PeriodicalIF":2.5,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144957712","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":"Changes in the public IgM repertoire and its idiotypic connectivity in Alzheimer's disease and frontotemporal dementia","authors":"Shina Pashova-Dimova ,&nbsp;Peter Petrov ,&nbsp;Sena Karachanak-Yankova ,&nbsp;Diana Belezhanska ,&nbsp;Yavor Zhelev ,&nbsp;Shima Mehrabian ,&nbsp;Draga Toncheva ,&nbsp;Lachezar Traykov ,&nbsp;Anastas Pashov","doi":"10.1016/j.jneuroim.2025.578775","DOIUrl":"10.1016/j.jneuroim.2025.578775","url":null,"abstract":"<div><div>Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative disorders. Early diagnosis is challenging due to the lack of definitive biomarkers and reliance on invasive procedures. Immune biomarkers, particularly those reflecting the interaction between the central nervous system (CNS) and the peripheral immune system, have shown promise for non-invasive detection through blood samples. This study investigates the reactivity of serum IgM and IgG from AD and FTD patients against a library of mimotopes representing public IgM reactivities in healthy donors. Serum samples from AD, FTD, and other neurodegenerative dementias (ND) and controls were tested on peptide microarrays. The samples were pooled to mitigate individual variability. The reactivity data were analyzed using graphs to represent the cross-reactivity networks. The analysis revealed distinct reactivity patterns for the studied groups. Public IgM reactivities showed significant correlations with neurodegenerative conditions, with AD and FTD exhibiting loss or gain of specific IgM reactivities. Graph analysis highlighted significant differences between disease and control groups in graph density, clustering, and assortativity parameters. Mimotopes of IgM reactivities lost in dementia, particularly in AD, exhibited significant homology to HCDR3 sequences of human antibodies. Furthermore, clusters of reactivities showed significant distinctions between AD and FTD, with IgG reactivities providing additional differentiation. Several self-proteins related to neurodegeneration proved to have sequences homologous to disease-associated mimotopes. Interestingly, the beta-propeller signature sequence YWTD found in ApoE's receptor LRP1 proved a characteristic epitope for IgG in FTD but not AD. At the same time, the respective public gM mimotope YWTDSSR coincides with a highly conserved sequence in many microorganisms and sequences found in human HCDR3. Thus, the public IgM repertoire, characterized by its broad reactivity and inherent autoreactivity, offers valuable insights into the immunological alterations in neurodegenerative diseases. The study supports the potential of IgM and IgG reactivity profiles as another compartment of non-invasive biomarkers for early diagnosis and differentiating AD and FTD.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578775"},"PeriodicalIF":2.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267109","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":"ITPR1 autoantibody-associated autoimmunity as a cause of newly emerging cognitive decline mimicking Alzheimer's disease: Case report and brief review of the literature.","authors":"Nicolas Kunath, Hermod Arne Bollandsås Ramfjord, Elisabeth Volden Kvisvik, Marton Konyves-Kolonics, Gøril Rolfseng Grøntvedt, Irina I Serysheva, Lars Komorowski, Brigitte Wildemann, Sven Jarius","doi":"10.1016/j.jneuroim.2025.578774","DOIUrl":"https://doi.org/10.1016/j.jneuroim.2025.578774","url":null,"abstract":"<p><strong>Background: </strong>Since its first description in 2014, anti-inositol 1,4,5-trisphosphate receptor type 1 (ITPR1, also termed IP3R1) autoimmunity has been recognized as causing a clinically heterogeneous spectrum of symptoms. While first described in patients with autoimmune cerebellar ataxia, this facultative paraneoplastic disease has been associated also with peripheral neuropathy, dysautonomia, sleep disorders, neuropsychiatric/psychotic symptoms, and cognitive decline.</p><p><strong>Methods: </strong>Retrospective case study.</p><p><strong>Results: </strong>We report the case of a 58-year-old patient who was admitted with acute confusion, rapidly progressive cognitive decline, and hallucinations. A history of mild cognitive impairment over several years and low cerebrospinal fluid (CSF) amyloid beta-42 and elevated CSF tau protein were suggestive of Alzheimer's disease (AD). However, pleocytosis, intrathecal IgG synthesis and blood-CSF barrier dysfunction prompted screening for antineuronal antibodies, which revealed ITPR1-IgG1/anti-Sj antibodies in both serum and CSF. Brain MRI showed limbic hyperintensities and hippocampal atrophy. No neoplastic disease was found. Immunosuppressive treatment stabilized the disease course but did not lead to symptom improvement.</p><p><strong>Conclusions: </strong>This case underscores the clinical importance of CSF analysis and testing for anti-neural autoantibodies, including less common reactivities, in case of rapid cognitive decline even in patients with known or suspected neurodegenerative disease, such as AD, with ITPR1 representing a novel autoimmune target antigen.</p>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"578774"},"PeriodicalIF":2.5,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280503","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":"Role of antibodies in immune checkpoint inhibitor–related CNS toxicities: insights from challenging clinical cases","authors":"Jeanne Benoit ,&nbsp;Bastien Joubert ,&nbsp;Alberto Vogrig","doi":"10.1016/j.jneuroim.2025.578778","DOIUrl":"10.1016/j.jneuroim.2025.578778","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment yet are increasingly associated with neurological immune-related adverse events (n-irAEs), which can affect any part of the nervous system. Accurate diagnosis is often challenging due to overlapping features with classical paraneoplastic neurological syndromes (PNS) and autoimmune encephalitis (AE). They may also resemble other neurological conditions, including demyelinating diseases. In this review, we present four illustrative cases of post-ICI n-irAEs involving the central nervous system (CNS). Through these cases and accompanying commentaries providing a critical appraisal of the current literature, we highlight the diagnostic, therapeutic, and prognostic challenges associated with these presentations. We emphasize both the role and limitations of neuronal antibody testing. This review stresses the need for rigorous clinical phenotyping, comprehensive immunological screening, and multidisciplinary management to improve early recognition of these complex and often severe complications and guide future therapeutic strategies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578778"},"PeriodicalIF":2.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267858","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":"The hidden toll: Atrophy of key central nervous system relays in African American women with multiple sclerosis","authors":"Nabeela Nathoo ,&nbsp;Nur Neyal ,&nbsp;Jiye Son ,&nbsp;Christopher G. Schwarz ,&nbsp;Elizabeth J. Atkinson ,&nbsp;Holly A. Morrison ,&nbsp;June Kendall Thomas ,&nbsp;John D. Port ,&nbsp;Kejal Kantarci ,&nbsp;Orhun H. Kantarci ,&nbsp;Burcu Zeydan","doi":"10.1016/j.jneuroim.2025.578776","DOIUrl":"10.1016/j.jneuroim.2025.578776","url":null,"abstract":"<div><h3>Background</h3><div>African American persons with MS (AApwMS) have more aggressive clinical and imaging outcomes than White American pwMS (WApwMS), including lower brain and spinal cord (SC) volumes. However, imaging studies are lacking considering the effects of sex, race, and ethnicity together.</div></div><div><h3>Objective</h3><div>Compare MS clinical and imaging features among AApwMS and WApwMS, incorporating the modifying effects of sex, race, and ethnicity.</div></div><div><h3>Methods</h3><div>Clinical variables and MRI were obtained for AApwMS and WApwMS.</div></div><div><h3>Results</h3><div>Thirty-five MRIs in 28 AApwMS (61 % female) and 255 MRIs in 91 WApwMS (68 % female) were evaluated. AApwMS had a shorter MS disease duration (median 5.9 years, IQR 2.7–13.1) compared to WApwMS (9.4 years, IQR 3.8–17.0; <em>p</em> = 0.034). Fewer AApwMS ever used disease modifying therapy (69 %) compared to WApwMS (92 %; <em>p</em> &lt; 0.001), while the likelihood of having progressive MS and developing severe disability were similar between groups (<em>p</em> &gt; 0.05). AA women with MS had smaller thalamus (<em>p</em> = 0.016), cerebellar grey matter (<em>p</em> = 0.025), and SC-C2 (<em>p</em> = 0.005) volumes than WA women with MS. Although multiple brain and SC regions were smaller in AA men than WA men with MS, the differences were not significant.</div></div><div><h3>Conclusion</h3><div>Interaction between sex, race, and ethnicity may influence differences in imaging metrics of key central nervous system relays, likely preceding clinical worsening in MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578776"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267110","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":"Over-excitation of tyrosine hydroxylase neurons in the paraventricular nucleus of the hypothalamus drives a neuroimmune positive feedback loop in rheumatoid arthritis","authors":"Hongxin Li ,&nbsp;Hongli Yu ,&nbsp;Xiuzhi Zhao ,&nbsp;Jiaxin Xu","doi":"10.1016/j.jneuroim.2025.578773","DOIUrl":"10.1016/j.jneuroim.2025.578773","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and pain, leading to a significant decline in patients' quality of life. Recent studies suggest that the central nervous system (CNS) may also contribute to disease progression by modulating autonomic and immune functions. However, the precise mechanisms underlying CNS involvement remain unclear.</div></div><div><h3>Objective</h3><div>This study aims to investigate the alterations in the functional state of tyrosine hydroxylase (TH) within the paraventricular nucleus (PVN) in RA and to explore their potential role in regulating peripheral immune responses.</div></div><div><h3>Methods</h3><div>An adjuvant-induced arthritis (AA) mouse model was employed. Changes in PVN-TH neuron excitability were assessed using double immunofluorescence staining, whole-cell patch-clamp recording, and in vivo calcium imaging. Chemogenetic inhibition of PVN-TH neurons was performed to evaluate behavioral manifestations of RA, such as paw swelling, paw withdrawal latency, and joint scoring, as well as the concentration of NE released from sympathetic nerve endings in the popliteal lymph nodes and subsequent immune responses in the popliteal lymph nodes, including T cell proliferation and dendritic cell activation.</div></div><div><h3>Results</h3><div>AA mice displayed pronounced hyperactivity of PVN-TH neurons, as indicated by increased c-Fos⁺ expression, higher action potential firing frequency, and elevated calcium signal amplitudes. Targeted inhibition of these neurons significantly reduced inflammatory symptoms and the concentration of NE released from sympathetic nerve endings in the popliteal lymph nodes, and decreased T cell proliferation and dendritic cell activation in the popliteal lymph nodes.</div></div><div><h3>Conclusion</h3><div>In the RA model, pathological hyperactivity exhibited by PVN-TH neurons may be involved in peripheral immune regulation through central sensitization and inflammatory signaling. These neurons may be key hubs driven by the central nervous system, providing new insights into neuroimmune mechanisms and potential targets for neuroimmunotherapy in RA.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578773"},"PeriodicalIF":2.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145267111","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":"Causal relationships between monocyte chemoattractant protein-1 levels and neuropsychiatric disorders: Evidence from large-scale genetic data","authors":"Yuyao He ,&nbsp;Wenyue Hu ,&nbsp;Yanliang Li ,&nbsp;Zhenyun Han","doi":"10.1016/j.jneuroim.2025.578767","DOIUrl":"10.1016/j.jneuroim.2025.578767","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the causal relationship between monocyte chemoattractant protein-1 (MCP-1) levels and risk of neuropsychiatric disorders (NPDs), including Alzheimer's disease (AD), vascular dementia (VD), depression, schizophrenia (SCZ), and anxiety disorders, using two-sample Mendelian randomization (MR).</div></div><div><h3>Methods</h3><div>Summary statistics from genome-wide association studies (GWAS) were utilized to examine the relationship between MCP-1 levels and NPDs. MCP-1 summary data were obtained from the IEU OpenGWAS database, while GWAS summary statistics for NPDs were primarily sourced from the FinnGen consortium, with additional replication datasets from the IEU OpenGWAS and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW) method, complemented by weighted median, MR-Egger regression, and both weighted and simple mode methods in bidirectional MR analyses. Heterogeneity was assessed using Cochran's Q test, and horizontal pleiotropy was evaluated using MR-Egger regression and the MR-PRESSO test. Results from multiple GWAS sources were synthesized using meta-analysis to provide robust and comprehensive estimates.</div></div><div><h3>Results</h3><div>In primary MR analysis, IVW results indicated a statistically significant association between elevated MCP-1 levels and increased risk of AD (OR: 1.108; 95 % CI: 1.003–1.224; <em>P</em>_<em>IVW</em> = 0.044) and SCZ (OR: 1.245, 95 % CI: 1.014–1.529, <em>P</em>_<em>IVW</em> = 0.036). No evidence of horizontal pleiotropy was observed (<em>P</em> &gt; 0.05), and leave-one-out sensitivity analysis supported the robustness of these findings. However, no causal associations were identified in replication MR analyses for MCP-1 with any of the NPDs (<em>P</em>_<em>IVW</em> &gt; 0.05). Meta-analysis further confirmed the significant association between MCP-1 levels and AD risk (OR: 1.096, 95 % CI: 1.017–1.182, <em>P</em> = 0.017), while no significant causal relationships were observed for the other NPDs.</div></div><div><h3>Conclusion</h3><div>Elevated MCP-1 levels are causally associated with Alzheimer's disease risk but not with other NPDs, indicating a disease-specific role and therapeutic potential in AD.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578767"},"PeriodicalIF":2.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258349","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":"Long non-coding RNA NEAT1 modulates microglial NLRP3 inflammasome activation","authors":"Bora Tastan ,&nbsp;Aysen Cotuk ,&nbsp;Burak I. Arioz ,&nbsp;Bilge Karacicek ,&nbsp;Beyza Ture ,&nbsp;Nilsu Tastan ,&nbsp;Sermin Genc","doi":"10.1016/j.jneuroim.2025.578770","DOIUrl":"10.1016/j.jneuroim.2025.578770","url":null,"abstract":"<div><div>Microglia, the resident macrophages in the central nervous system (CNS), play a fundamental role in maintaining CNS homeostasis and responding to immune challenges. Dysregulated microglial activation and subsequent neuroinflammation are associated with various CNS diseases. A key mechanism driving neuroinflammation is the activation of the NLRP3 inflammasome complex triggered by diverse molecular motifs. The microglial NLRP3 inflammasome activation has been implicated in a plethora of diseases, including cardiovascular, autoimmune, and neurodegenerative diseases. Long non-coding RNAs (lncRNAs), particularly Nuclear Enriched Abundant Transcript 1 (NEAT1), have emerged as essential players in gene regulation and inflammation. In this study, we investigated the role of NEAT1 in microglial NLRP3 inflammasome activation utilizing <em>in vitro</em> and <em>in vivo</em> models. Our <em>in vivo</em> studies showed that NEAT1 knockout alleviates NLRP3 inflammasome activation in LPS-injected NEAT1 KO mice. Additionally, our <em>in vitro</em> studies confirmed these findings, demonstrating that NEAT1 expression is upregulated upon NLRP3 inflammasome activation in microglia. Further experiments revealed that NEAT1 depletion with siRNA significantly attenuated NLRP3 inflammasome activation and the release of pro-inflammatory cytokine IL-1β. Mechanistically, we found that NEAT1 interacted with RNA-binding proteins to regulate NLRP3 inflammasome activation. Given the central role of microglial NLRP3 inflammasome activation in neuroinflammation, our findings elaborated the regulatory mechanisms involving NEAT1, thus offering potential therapeutic avenues for CNS disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"409 ","pages":"Article 578770"},"PeriodicalIF":2.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227060","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}