Journal of Neuroinflammation最新文献

{"title":"HMGB1-mediated endoplasmic reticulum stress in monocyte-derived dendritic cells regulates CD4+ T cell immune responses in myasthenia gravis.","authors":"Qing Zhang, Zhongya Gu, Yaxuan Li, Mengge Yang, Xue Ma, Xuanxuan Pan, Zhuajin Bi, Jing Lin, Mengcui Gui, Furong Wang, Min Zhang, Zhijun Li, Bitao Bu","doi":"10.1186/s12974-026-03908-x","DOIUrl":"10.1186/s12974-026-03908-x","url":null,"abstract":"<p><strong>Introduction: </strong>Myasthenia gravis (MG) is an autoimmune disorder characterized by immune dysregulation at the neuromuscular junction. Monocyte-derived dendritic cells (moDCs) are increasingly recognized as key drivers of MG pathogenesis; however, the mechanisms that govern their dysfunction remain incompletely understood.</p><p><strong>Methods: </strong>This study integrated human genetics, patient immunophenotyping, and therapeutic evaluation in the experimental autoimmune myasthenia gravis (EAMG) model. Monocytes were isolated and differentiated into moDCs to assess the effects of HMGB1 and its inhibitor, 18α-glycyrrhetinic acid (18α-GA), on the expression profiles, phenotypes, and functions of moDCs. Therapeutic efficacy was further assessed in EAMG using 18α-GA, HMGB1 neutralizing antibody, and adoptive transfer of 18α-GA-induced tolerogenic moDCs.</p><p><strong>Results: </strong>Mendelian randomization (MR) analyses revealed bidirectional causality between MG and moDCs. MG patients exhibited elevated plasma HMGB1 levels and mature phenotypes of moDCs. Mechanistically, HMGB1 activated the IRE1α/XBP1 and NF-κB pathways in moDCs through the engagement of TLR4, thereby inducing endoplasmic reticulum (ER) stress, promoting the activation of moDCs, and driving an imbalance in CD4+ T cell immune responses. Through a multitargeted mechanism of action, 18α-GA effectively inhibited both the IRE1α/XBP1 and NF-κB pathways in moDCs, thereby blunting ER stress and driving the differentiation of moDCs toward tolerogenic phenotypes. The minimal effective dose of 18α-GA alleviated EAMG by counteracting HMGB1-driven, moDC-mediated CD4+ T cell dysfunction, and showed better therapeutic performance compared with HMGB1 neutralizing antibody. Moreover, the adoptive transfer of 18α-GA-induced tolerogenic moDCs was effective in treating EAMG.</p><p><strong>Conclusions: </strong>HMGB1-mediated ER stress reprogrammed moDCs via the IRE1α/XBP1 and NF-κB pathways to promote pathogenic CD4+ T cell responses in MG. Targeting the HMGB1-ER stress axis in moDCs could restore immune balance and represent a promising therapeutic strategy for MG.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13508458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A brain-lung circuit drives LPS-induced lung injury via sympathetic neutrophil axis.","authors":"Shichun Ren, Shuo Yang, Baotong Liu, Qian Zhang, Zhenzhen Zhao, Yan Meng, Qi Shao, Xiaoming Deng, Jinjun Bian, Li Cao, Fengfeng Mo, Jiafeng Wang","doi":"10.1186/s12974-026-03914-z","DOIUrl":"10.1186/s12974-026-03914-z","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a fatal complication of sepsis. However, the neural mechanisms underlying the exacerbation of pulmonary inflammation during systemic infection remain largely undefined. We employed an intraperitoneal lipopolysaccharide (LPS)-induced systemic inflammatory lung injury model and found that systemic inflammation strongly activates corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN), whereas bilateral subdiaphragmatic vagotomy abolished this response. Chemogenetic inhibition of CRH^PVN neurons alleviated lung injury and the formation of neutrophil extracellular traps (NETs), whereas chemogenetic activation of CRH^PVN neurons exacerbated pathological damage through sympathetic efferent signaling. Additionally, in patients with septic ARDS, β2-adrenergic receptor (ADRB2) expression was upregulated on neutrophils, and ADRB2 signaling delayed neutrophil apoptosis through the PI3K/Akt pathway, whereas ADRB2 blockade promoted neutrophil apoptosis and attenuated lung injury. In summary, we delineate a dysregulated neuroimmune axis in LPS-induced lung injury: systemic inflammatory signals activate the vagal afferent-PVN-sympathetic circuit, which in turn drives a neutrophil-mediated ADRB2-PI3K/Akt signaling pathway that amplifies lung injury. Our study reveals a mechanistic basis for neuroregulatory intervention and indicates that targeting this Brain-lung pathway may offer new therapeutic strategies for ARDS.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared transcriptomic signatures in perilesional and contralesional cortex after ischemic stroke.","authors":"Dene Betz, Victoria A Alers, Matthew Kenwood, Kielen R Zuurbier, Rebeca Coimbra, Priscilla Rhoton, Erik J Plautz, Peter M Douglas, Denise M O Ramirez, Ann M Stowe, Mark P Goldberg","doi":"10.1186/s12974-026-03885-1","DOIUrl":"10.1186/s12974-026-03885-1","url":null,"abstract":"<p><p>Stroke induces a transient period of heightened plasticity during which functional recovery is most pronounced. Experimental models have identified repair-associated processes in both the ipsilesional and contralesional cortex, indicating that stroke recovery involves regions both remote and near the lesion. However, most transcriptional studies have focused on the infarct core and peri-lesional cortex (PLC), leaving it unclear whether comparable molecular responses occur in the contralesional cortex (CLC), a region that undergoes substantial remodeling in the absence of direct tissue injury, necrosis, or widespread cellular infiltration. In addition, potential sex-dependent differences in these responses remain incompletely defined, despite known influences of biological sex on post-stroke inflammation and vascular remodeling. To address these gaps, we performed bulk RNA-sequencing of the PLC and CLC at 7 days after photothrombotic stroke, a subacute time point associated with the initiation of repair, in male and female mice. Despite distinct positions relative to the lesion, both regions exhibited robust upregulation of inflammatory signaling, including cytokine-, astrocyte-, and myeloid-lineage-associated pathways. The CLC did not demonstrate a distinct region-specific transcriptional profile; instead, shared signatures between PLC and CLC included genes strongly associated with reactive microglial phenotypes. This shared neuroinflammatory response was largely conserved across sexes. Consistent with these findings, male and female mice exhibited comparable corticospinal tract axonal sprouting originating from the CLC at 6 weeks post-stroke. Together, these findings support a shared neuroinflammatory transcriptional response as a prominent early feature of cortical regions associated with post-stroke plasticity.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte β-catenin suppression by HIV and methamphetamine drives senescence and dysfunction of MEGF10-dependent phagocytosis, neuronal support, and BBB integrity.","authors":"Arundhati Jana, Srinivas D Narasipura, James Szczerkowski, João I Mamede, Lena Al-Harthi","doi":"10.1186/s12974-026-03886-0","DOIUrl":"10.1186/s12974-026-03886-0","url":null,"abstract":"<p><p>Astrocytes are essential regulators of central nervous system (CNS) homeostasis, and their dysfunction can amplify neuroinflammation and neurodegeneration. HIV and methamphetamine (Meth) are known to downregulate β-catenin signaling and induce astrocyte senescence, but whether this senescent state is functionally pathogenic and contributes directly to neuroinflammatory processes remains unclear. Here, we investigated how senescent astrocytes respond across prototypical astrocytic functions.In vitro, human iPSC-derived astrocytes infected with HIV and/or exposed to Meth developed a senescence phenotype (increased p16^INK4A) accompanied by reduced expression of the phagocytic receptor MEGF10 and impaired engulfment of apoptotic neurons. HIV/Meth exposure also shifted astrocyte secretomes toward proinflammatory profiles (IL-6, CCL2, CXCL1, and ICAM-1), and astrocyte-conditioned media decreased neuronal PSD95 and NFL and disrupted endothelial adherens and tight junction proteins (VE-cadherin, occludin, claudin-5), resulting in increased monocyte transmigration. Mechanistically, pharmacologic activation or lentiviral expression of active β-catenin protected astrocytes from senescence, preserving MEGF10 expression and phagocytic capacity under HIV/Meth exposure, while MEGF10 overexpression independently restored phagocytosis. In a human-mouse chimera model (NSG mice xenotransplanted with human iPSC-derived astrocytes), HIV infection and/or Meth administration increased p16^INK4A and reduced MEGF10 expression in engrafted human astrocytes, recapitulating in vitro findings.Together, these studies demonstrate that HIV and Meth suppress β-catenin signaling to drive a functionally disruptive astrocyte senescence program linked to impaired MEGF10-dependent phagocytosis, diminished neuronal support, and compromised blood-brain barrier integrity. Restoring β-catenin signaling and preserving MEGF10 function emerge as rational strategies to prevent astrocyte-driven neuroinflammation and neuropathogenesis in HIV/Meth co-morbidity.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13712060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nipah virus infects the brain and triggers neuronal and glial damage in a hamster model.","authors":"Karl Valerdi, Takeshi Saito, Ruchi Paroha, Kirsten Littlefield, Jessica Plante, Kenneth Plante, Silvana Valdebenito, Junki Maruyama, Eliseo Eugenin","doi":"10.1186/s12974-026-03901-4","DOIUrl":"10.1186/s12974-026-03901-4","url":null,"abstract":"<p><p>Nipah virus (NiV) is distributed in South-East Asia and the Western Pacific, with currently active outbreak sites. NiV causes an acute febrile illness with high mortality (40-70%), encephalitis, and long-term disability among survivors. Currently, there are no effective therapeutic or preventive interventions, and its potential for explosive spread resulted in its designation as a pathogen of international epidemiological concern. However, the pathophysiology of NiV-induced encephalitis remains unclear. Using a hamster model of NiV infection, we demonstrated that NiV targets several brain areas, such as the cortex and the hippocampus, infecting neurons, astrocytes, and blood-brain barrier cells. NiV infection also induced glial activation, including both microglia and astrocytes, leading to vascular and neuronal compromise and parenchymal lesions. Overall, NiV demonstrates a marked tropism for the central nervous system, resulting in major damage and death.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13495180/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroglial P2Y₁ receptor signalling differentially contributes to inflammatory neurodegeneration.","authors":"Charlotte Schubert, Ricardo Lopes Fonseca, Alexandros Hadjilaou, Vanessa Vieira, Karoline Degenhardt, Anna Lena Seemann, Alice Hakimy, Jana K Sonner, Peter Ludewig, Tim Magnus, Marion Schneider, Christa E Müller, Daniela Hirnet, Manuel A Friese","doi":"10.1186/s12974-026-03904-1","DOIUrl":"10.1186/s12974-026-03904-1","url":null,"abstract":"<p><p>Extracellular adenosine triphosphate (ATP) and diphosphate (ADP) act as key signalling molecules in the central nervous system (CNS) and regulate neuroinflammatory responses through purinergic receptors. Although astrocytes and neurons undergo profound changes in signalling and metabolism during inflammation, the contribution of specific purinergic pathways to inflammation-induced neurodegeneration remains unclear. Here we show that the ADP/ATP-activated Gq-coupled receptor P2Y₁ drives astrocyte-mediated neurotoxicity in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS). Using plasma membrane-targeted luciferase reporter mice, we demonstrate that extracellular ATP levels are increased during acute EAE. This was accompanied by elevated astrocytic P2ry1 expression, which is also observed in inflammatory MS lesions. In vivo, pharmacological inhibition or astrocyte-specific deletion of P2Y₁ reduced disease severity, astrocytosis, and neuronal loss, whereas neuron-specific deletion exerted only modest effects. Mechanistically, astrocytic P2Y₁ signalling promoted cytokine-induced ERK activation, inflammatory gene expression, and metabolic reprogramming in vitro. In contrast to supernatants from stimulated P2Y₁-deficient astrocyte culture, supernatants derived from stimulated P2Y₁-proficient astrocytes reduced neuronal viability, demonstrating neurotoxic effects mediated by astrocyte-derived factors. In contrast, neuronal P2Y₁ signalling primarily contributed to oxidative stress and mitochondrial dysfunction. Together, these findings identify astrocytic P2Y₁ as a key regulator of neuroinflammatory damage and a potential therapeutic target.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":"23 1","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13263940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TREM2 restrains myeloid inflammasome activation to protect against photoreceptor degeneration.","authors":"Tianxi Wang, Liyun Su, Manon Szczepan, Xingyan Wang, Austin T Gregg, Jessica Guo, Lois E H Smith, Ye Sun","doi":"10.1186/s12974-026-03903-2","DOIUrl":"10.1186/s12974-026-03903-2","url":null,"abstract":"<p><p>Myeloid cells, including infiltrating macrophages and resident microglia, are critical regulators of retinal homeostasis and respond rapidly to photoreceptor stress. Dysregulated myeloid responses, however, can exacerbate retinal degeneration. Triggering receptor expressed on myeloid cells 2 (TREM2) modulates phagocytosis, metabolism, and inflammatory signaling, yet its role in retinal degeneration remains incompletely understood. Here, we investigated TREM2 function in the retinal degeneration 10 (rd10) mouse model of inherited retinal degeneration, characterized by progressive photoreceptor loss and robust myeloid cell activation. TREM2 expression was upregulated in degenerating retinas, and global TREM2-deficiency in rd10 mice exhibited accelerated photoreceptor cell death, reduced outer nuclear layer thickness, disrupted retinal pigment epithelium integrity, and altered microglial spatial dynamics. Single-cell transcriptomics revealed that TREM2-positive microglia express APOE-associated and interferon-primed programs. Global TREM2 deficiency was associated with increased inflammasome-related signaling in retinal myeloid cells, including elevated cleaved caspase-1, cleaved gasdermin D, and mature interleukin-1β, linking amplified immune priming to pyroptotic signaling. Genetic or pharmacological inhibition of gasdermin D significantly mitigated photoreceptor loss in global TREM2-deficient rd10 retinas, demonstrating a functional contribution of inflammasome-associated responses to disease exacerbation. Together, these findings support a protective role for TREM2-associated immune regulation in the degenerating retina and identify downstream inflammasome pathways as potential therapeutic targets in retinal degenerative diseases.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148251851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The active role of pulmonary immunity in ischaemic stroke.","authors":"Junyi Wu, Yikun Gao, Yilin Li, Jiayan Gu, Xiaoting Li, Jin Wang, Xiaoxing Xiong, Lijuan Gu","doi":"10.1186/s12974-026-03907-y","DOIUrl":"10.1186/s12974-026-03907-y","url":null,"abstract":"<p><p>Previous stroke studies have mostly regarded the lungs as passively damaged target organs, and in clinical practice in the context of stroke, the role of the lungs has been habitually limited to secondary complications such as stroke-associated pneumonia or neurogenic pulmonary oedema. However, recent studies have indicated that the lung plays a more active and central role in the pathophysiology of stroke. In this review, we propose and systematically elaborate on an emerging concept: the lung, as one of the largest immune organs in the body, functions as an active initiator and amplifier of systemic inflammation and neuroinflammation following stroke. Stroke \"remotely primes\" the unique immune reservoir of the lung (such as marginated pool neutrophils and resident macrophages) via neural and humoral pathways, leading to the rapid activation and release of these cells into the circulation. Activated pulmonary immune cells not only possess an enhanced capacity for brain homing but also produce large amounts of proinflammatory mediators, establishing a self-amplifying inflammatory cycle that significantly worsens neurological outcomes. Furthermore, we explore how advanced age and metabolic comorbidities, such as diabetes, pathologically remodel the pulmonary immune baseline, thereby increasing susceptibility to this self-amplifying cascade. By highlighting the current translational gap between preclinical models and human clinical cohorts, we propose that elevating the lung from a therapeutic bystander to a core intervention target provides a novel \"brain-lung coprotection\" strategy, which may offer a new perspective for optimizing the comprehensive clinical management of ischaemic stroke.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C1q-CD44 interactions regulate microglial phagocytosis, proliferation, and migration.","authors":"Pooja S Sakthivel, Alyssa J Villegas, Anita Lakatos, Meghana Kaipa, Julian M Lopez, Ashley Ling, Zeina H Elrachid, Josh Karam, Aileen J Anderson","doi":"10.1186/s12974-026-03892-2","DOIUrl":"10.1186/s12974-026-03892-2","url":null,"abstract":"<p><p>Microglia, the immune cells of the central nervous system (CNS), quickly respond to neurodegeneration by proliferating and migrating to areas of disease, phagocytosing debris, and releasing cytokines to initiate inflammation. Critically, the mechanisms underlying these microglial functions remain only partly understood. One molecular regulator of interest is complement protein C1q, the initiator molecule of the complement cascade that increases 300-fold in healthy aging and accumulates with neurodegeneration. We have previously reported that exogenous C1q treatment alters inflammatory gene expression and cell function in human induced pluripotent stem cell-derived microglia (iMG). Here, we test the hypothesis that C1q induced cell changes are modulated by novel C1q receptor, CD44. We first confirmed expression of five novel C1q receptors at the RNA and protein levels, and then validated C1q-receptor binding on the iMG cell surface using proximity ligation assay. Based on these results, we selected CD44 as an initial target and generated CD44 knockout iMG to test the role of CD44 in the iMG response to C1q. We demonstrate that C1q-CD44 interactions regulate changes in microglial phagocytosis, proliferation, and migration. These data suggest C1q interacts with CD44 to modulate microglial functions that are critical to health and disease, thus informing future directions to test whether these interactions are altered in neurodegenerative disease.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13483542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian gatekeepers of the gut-brain-immune axis: implications for neuroinflammation and neurodegeneration.","authors":"Wai-Yin Cheng, Po-Lam Chan, Man-Ka Chan, Jiaying Xu, Ka-Hing Wong, Raymond Chuen-Chung Chang","doi":"10.1186/s12974-026-03899-9","DOIUrl":"10.1186/s12974-026-03899-9","url":null,"abstract":"<p><p>Circadian rhythms, primarily regulated by light-dark cycles, play a crucial role in maintaining physiological health, including metabolism and immune responses. Evidence shows that circadian rhythms are involved in modulating gut microbiota composition, peripheral and central immune systems, and neurodegenerative disease progression. Recent research has illuminated the complex interplay between circadian rhythms and the gut microbiota-immune-brain axis. This review examines the bidirectional relationship between circadian rhythms and gut microbiota, and explores how this interaction influences brain function through the gut-brain axis, with particular focus on neuroinflammation and neurodegeneration. We aim to provide novel insights that could inform therapeutic strategies to prevent or slow down the progression of neurodegenerative diseases through circadian rhythm modulation.</p>","PeriodicalId":16577,"journal":{"name":"Journal of Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13491710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}