Inflammation Research最新文献

{"title":"Misplaced DNA sensing in intervertebral disc degeneration: mitochondrial stress, sterile inflammation, pyroptosis, and DNA clearance.","authors":"Hongtao Li, Jiacheng Zheng, Guangyi Yang, Bochen Peng, Hanbin Liu, Liguo Zhu, Changxiao Han, Minshan Feng","doi":"10.1007/s00011-026-02392-6","DOIUrl":"https://doi.org/10.1007/s00011-026-02392-6","url":null,"abstract":"<p><p>Intervertebral disc degeneration (IVDD) links cellular stress to persistent sterile inflammation, but the initiating role of misplaced DNA remains uncertain. This review examines mitochondrial DNA (mtDNA) and other self-DNA through a source-compartment-sensor-output framework. Cytosolic DNA can engage cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling, whereas endolysosomal DNA can engage Toll-like receptor 9 (TLR9). Disc-cell experiments and induced animal models support contributions to inflammatory signaling and pyroptotic injury. Genetic findings vary across aging models, limiting universal claims about STING-driven degeneration. We distinguish resident-cell responses from immune-cell recruitment, pathological stress from physiological adaptation, and experimental pathway dependence from disease initiation. We also assess extracellular nucleic-acid capture as preliminary intervention evidence without assuming that native matrix retention or endogenous nuclease failure has been established. The framework identifies where direct disc evidence supports a mechanism and where trafficking, causality or clearance remains unresolved. Priorities include source-selective perturbation, temporal and compartment-resolved measurements, and independent structural and pain-related outcomes. Clinical translation requires validation beyond preclinical structural improvement.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zyxin protects against hypertensive nephropathy by restraining FAK/Skp2-CDK8/YAP signaling in tubular epithelial cells.","authors":"Wei Huang, Yi-Yuan Chen, Yu-Mei Wang, Si-Jia Du, Yu Hao, Chun Zhang, Xiao-Li Zhang, Fang-Fang He","doi":"10.1007/s00011-026-02373-9","DOIUrl":"https://doi.org/10.1007/s00011-026-02373-9","url":null,"abstract":"<p><strong>Background: </strong>Tubulointerstitial fibrosis and inflammation are hallmark pathological features of hypertensive nephropathy (HN), yet the underlying molecular mechanisms remain elusive. Zyxin, a focal adhesion protein, has been implicated in hypertension-related pathologies, but its specific role in HN-induced tubulointerstitial injury remains undefined.</p><p><strong>Methods: </strong>An HN murine model was established via a multi‑hit DOCA/Ang II + uninephrectomy + high salt approach. Intrarenal zyxin was overexpressed using adeno-associated virus. In vitro, HK-2 cells were stimulated with Ang II, and zyxin levels were modulated via lentiviral transduction. Renal function, inflammation, and fibrosis were evaluated through biochemical assays and molecular signaling analysis.</p><p><strong>Results: </strong>Zyxin was significantly downregulated in the renal tubules of HN mice and Ang II-treated HK-2 cells. Zyxin overexpression significantly improved renal function and attenuated tubulointerstitial injury, with a representative reduction of approximately 40% in the expression of fibrotic markers. These protective effects occurred independently of blood pressure changes. Mechanistically, zyxin reduction is linked to Ang II-induced calpain activation. The resulting zyxin depletion potentially disinhibits the FAK/Skp2 axis and enhances CDK8/YAP signaling, which may contribute to renal inflammation and interstitial fibrosis.</p><p><strong>Conclusions: </strong>These findings support a model in which zyxin acts as a protective factor in the renal tubules during HN, suggesting its potential as a novel therapeutic target.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitor-associated myocarditis: clinical and mechanistic insights.","authors":"Heng Liu, Weili Li, Yunxia Wu, Nannan Tan, Jingmei Zhang, Yawen Zhang, Guanjing Ling, Yilin Li, Zhishu Tang, Wei Wang, Yong Wang","doi":"10.1007/s00011-026-02397-1","DOIUrl":"https://doi.org/10.1007/s00011-026-02397-1","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can cause immune-related adverse events, including potentially severe cardiovascular toxicities. Although rare, immune checkpoint inhibitor-associated myocarditis (ICIM) can present early and may be rapidly fatal, posing a significant challenge at the crossroads of oncology, immunology, and cardiology.</p><p><strong>Purpose: </strong>This review synthesizes emerging clinical and experimental evidence to refine understanding of risk factors for immune checkpoint inhibitor-associated myocarditis and to outline a practical clinic-to-bench framework linking surveillance and diagnostic decision-making to pathogenic cellular programs.</p><p><strong>Conclusions: </strong>We highlight the cardiac immune microenvironment as a network of multicellular interactions in which cytotoxic T cells and inflammatory myeloid subsets engage with cardiomyocytes, endothelial cells, and fibroblasts through reinforcing feedback loops. Specifically, interferon-γ (IFN-γ)-driven myeloid activation and chemokine programs (CXCR3-CXCL9/10, CXCL16-CXCR6) coordinate immune cell trafficking and promote tissue injury, while stress-related cell death pathways can trigger innate immune sensing via the cGAS-STING axis. Current management remains centered on early recognition and corticosteroid-based immunosuppression, but emerging mechanistic insights reveal opportunities to improve therapy by targeting immune cell trafficking and inflammatory amplification pathways. Together, these advances support a more integrated cardio-oncology approach to ICIM, in which mechanistic insights inform risk stratification, earlier diagnosis, and the development of more precise immunomodulatory therapies.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The aminoadamantane derivative 3F2 modulates monocyte and NK cell activation and restores immune mediators altered by Monkeypox virus stimuli.","authors":"Thaís de Fátima da Silva Moraes, Geovane Marques-Ferreira, Ágata Lopes-Ribeiro, Erik Vinicius de Sousa Reis, Gabriela Lorrany Aparecida Azevedo, Victor de Melo Rocha, Marília Bueno da Silva Menegatto, Felipe Alves Clarindo, Caio Wilker-Teixeira, Laura Cardoso Corrêa-Dias, Nathália Evelyn Morais Costa, Luan Ramalho Pinheiro, Adriano de Paula Sabino, Erna Geessien Kroon, Ângelo de Fátima, Jordana Grazziela Alves Coelho-Dos-Reis","doi":"10.1007/s00011-026-02387-3","DOIUrl":"10.1007/s00011-026-02387-3","url":null,"abstract":"<p><p>The monkeypox virus (MPV) is known to employ multiple immune evasion strategies that compromise antiviral defenses and disrupt immune homeostasis. Here, we characterized the immune responses induced by stimulation with inactivated MPV and evaluated the ability of aminoadamantane (AMA) and its derivative, 3F2, to restore immune function. Peripheral blood mononuclear cells that were stimulated with MPV exhibited altered activation in a subset of monocytes, along with suppressed activation of natural killer (NK) and natural killer T (NKT) cells. MPV stimulation also led to significant changes in the levels of immunosoluble mediators, including reductions in chemokines and cytokines that are crucial for antiviral defense and immune regulation. Treatment with 3F2 proved to be more effective than AMA, resulting in significantly higher levels of CCL2, CXCL8, IFN-γ, IL-12(p40), IL-15, IL-5, and essential growth factors such as VEGF and NGF-β. Furthermore, 3F2 treatment partially reverses monocyte activation and re-establishes NK and NKT cell function. The current results indicate that 3F2 can control inflammation while preserving antiviral responsiveness. These findings demonstrate that inactivated MPV stimuli profoundly modulates innate immune activation and identify 3F2 as a promising immunomodulatory candidate capable of partially restoring immune responses altered by viral particle stimulation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM36 catalyzes K63-linked ubiquitination of TAK1 to drive septic inflammation.","authors":"Shijie Song, Dingnai Nie, Zulaya Abudureyimu, Yijin Kuang, Wen Li, Xiaodan Yang, Qiao Ling, Junli Sheng, Huiru He, Xiaolong You, Suwan Wu, Wenhao Lu, Yuling Fu, Shouhai Wu, Kang Chen, Shengfeng Hu","doi":"10.1007/s00011-026-02393-5","DOIUrl":"https://doi.org/10.1007/s00011-026-02393-5","url":null,"abstract":"<p><strong>Background: </strong>The Toll-like receptor 4 (TLR4) pathway is critical for initiating innate immunity; however, its dysregulation drives pathological inflammation in diseases such as sepsis.</p><p><strong>Methods: </strong>In the present study, we utilized septic patients, lipopolysaccharide (LPS)-induced mouse models, and LPS-treated mouse macrophages as well as human THP-1-derived macrophages to investigate the potential functions and molecular mechanisms of TRIM36 in sepsis.</p><p><strong>Results: </strong>Here, we identify tripartite motif protein 36 (TRIM36) as a key positive regulator that amplifies TLR4 signaling. TRIM36 expression was robustly upregulated in macrophages upon lipopolysaccharide (LPS) challenge. Mechanistically, TRIM36 directly bound to TGF-β-activated kinase 1 (TAK1) and catalyzed its K63-linked ubiquitination, a prerequisite for the activation of TAK1 and the downstream nuclear factor-κB (NF-κB) pathway. Functionally, genetic ablation of Trim36 in mice attenuated hypothermia, improved survival, and reduced cytokine production in an LPS-induced sepsis model. Consistently, in vitro knockdown of TRIM36 in human macrophages blunted LPS-induced signaling and the secretion of proinflammatory mediators. Furthermore, analysis of a public transcriptomic dataset revealed that elevated TRIM36 levels were associated with non-survival in patients with sepsis.</p><p><strong>Conclusions: </strong>Collectively, our findings establish TRIM36 as a critical amplifier of TLR4-induced hyperinflammation and highlight its potential as a therapeutic target for sepsis.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-1β/IL-6 inflammatory crosstalk drives DNA methylation and histone remodeling associated with cytokine induced senescence in luminal breast cancer.","authors":"Satyajit Dey Pereira, Kanaka Sai Ram Padam, Padival Shruptha, Aditi Atreya, Manjunath B Joshi, Kapaettu Satyamoorthy","doi":"10.1007/s00011-026-02391-7","DOIUrl":"10.1007/s00011-026-02391-7","url":null,"abstract":"<p><strong>Background: </strong>Chronic inflammation exerts paradoxical effects in breast cancer, inducing growth arrest while sustaining tumor progression. However, how autocrine and paracrine inflammatory cytokine induced senescence integrates with tumor-promoting behaviour remains unclear. Here, we identify a reciprocal IL-1β/IL-6 circuit that links inflammatory cues, epigenetic remodeling and cytokine induced senescence in luminal breast cancer cells.</p><p><strong>Methods: </strong>Following treatment with IL-1β and IL-6, MCF-7 cells were examined using cell-cycle, apoptosis, reactive oxygen species flow cytometry assays, and senescence assays; RNA sequencing; global DNA methylation quantification; methylation-specific PCR; ChIP-qPCR for histone marks; cytokine ELISA; and western blotting for DNMTs and STAT3/AKT/NF-κB signaling proteins. The kinetics of IL-1β and IL-6 signaling were examined using receptor antagonism and pharmacological inhibition.</p><p><strong>Results: </strong>IL-1β induced senescence characterized by G₀/G₁ arrest, elevated SA-β-gal activity, ROS accumulation and absence of apoptosis. Transcriptomic profiling revealed cell-cycle regulator repression, enrichment of senescence-associated signatures and a pro-inflammatory secretory phenotype. Mechanistically, IL-1β induced increased DNMT1 and DNMT3A expression, elevated global DNA methylation, induced promoter-specific DNA methylation (IL-15, HMGB2) and histone mark remodeling (IL-6, IL1RN, BCL2,BAX) at inflammatory, senescence, and apoptotic loci. IL-1 receptor antagonism attenuated these effects. IL-6 induced downstream of IL-1β, in turn activated STAT3, increased DNMT1 and DNMT3B expression, amplified IL-1β expression and tumor-promoting phenotypes, while sustaining the IL-1β induced senescence state. IL-6R blockade disrupted this axis and reduced tumor-promoting effects.</p><p><strong>Conclusion: </strong>An IL-1β/IL-6 inflammatory loop drives epigenetic remodeling associated with cytokine induced senescence while promoting tumor-supportive signaling. IL-1β initiates the senescence program, whereas IL-6 reinforces and sustains this state through STAT3/DNMT signaling, highlighting inflammatory cytokine signaling pathways as potential therapeutic targets for breast cancer therapy.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imbalance of renin-angiotensin system in calcium oxalate crystals-induced renal oxidative stress and autophagy.","authors":"Sen-Yuan Hong, Lin-Tao Miao, Shao-Gang Wang, Yuan-Yuan Yang, Bao-Long Qin","doi":"10.1007/s00011-026-02389-1","DOIUrl":"https://doi.org/10.1007/s00011-026-02389-1","url":null,"abstract":"<p><strong>Background: </strong>Calcium oxalate (CaOx) stones are the most prevalent urological calculi with high incidence and recurrence. Effective preventive drugs remain lacking because of unclear pathogenesis. Although the imbalance of the dual renin-angiotensin system (RAS) axes is closely linked to oxidative stress and autophagy, its role in CaOx stone formation remains undefined.</p><p><strong>Methods: </strong>In vitro, human renal tubular epithelial cells were stimulated with CaOx crystals, with siRNA-mediated AT1R or MasR knockdown or pretreatment with Ang Ⅱ, Ang-(1-7), antioxidant Nacetylcysteine (NAC) or autophagy inhibitor 3-methyladenine (3-MA). RAS components, oxidative stress markers, autophagy-related proteins, stone-related proteins and crystal adhesion were detected. In vivo, a mouse CaOx stone model was induced by intraperitoneal glyoxylic acid injection, with adeno-associated virus-mediated AT1R or MasR knockdown. The above indicators and renal crystal deposition were evaluated.</p><p><strong>Results: </strong>CaOx crystals significantly activated the ACE/Ang Ⅱ/AT1R axis and inhibited the ACE2/Ang-(1-7)/MasR axis in vitro and in vivo, causing intrarenal RAS imbalance. CaOx crystals induced NOX2/4-mediated oxidative stress and AMPK/mTOR-dependent autophagy, which formed a mutually reinforcing loop to upregulate stone-related proteins (OPN, CD44, MCP-1). Activating the ACE/Ang Ⅱ/AT1R axis with Ang Ⅱ exacerbated these pathological changes, while AT1R knockdown alleviated them; conversely, activating the ACE2/Ang-(1-7)/MasR axis with Ang-(1-7) exerted protective effects, whereas MasR knockdown worsened injury. In vivo findings corroborated these results.</p><p><strong>Conclusion: </strong>The ACE/Ang Ⅱ/AT1R axis plays a pathogenic role in CaOx stone formation, whereas the ACE2/Ang-(1-7)/MasR axis exerts a protective effect. Restoring this intrarenal RAS balance represents a promising therapeutic strategy against CaOx stones.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing identifies a proinflammatory S100a8/a9⁺ macrophage subset contributing to acute kidney injury.","authors":"Ting Ren, Xinni Zhang, Jinghan Feng, Xiaoyan Wang, Zhouping Zou, Qi Zeng, Fangyuan Peng, Qiang Yang, Xiaoqiang Ding, Ping Jia","doi":"10.1007/s00011-026-02395-3","DOIUrl":"https://doi.org/10.1007/s00011-026-02395-3","url":null,"abstract":"<p><strong>Objective: </strong>Macrophages represent a heterogeneous cell population in the kidney. However, macrophage subsets and their role in endotoxemia-induced acute kidney injury (AKI) remain elucidated.</p><p><strong>Material and methods: </strong>Single-cell RNA sequencing was performed to identify macrophage subpopulations in mouse kidney following lipopolysaccharide (LPS) challenge. AKI was induced by LPS treatment or renal ischemia reperfusion injury in wild-type or S100a9^-/- mice. Silencing or overexpression of S100a9 was carried out to assess its function and contribution to LPS-induced inflammation and AKI. In addition, bone marrow cells from S100a9^-/- mice were injected into the recipient mice to determine the effect of S100a9 deletion in macrophage differentiation and renal inflammatory injury.</p><p><strong>Results: </strong>By using single-cell RNA sequencing, we identified a unique S100a8/a9⁺Ly6c^high proinflammatory macrophage subpopulation in mouse kidney following LPS challenge. LPS administration induced the infiltration of Ly6c⁺ macrophages into kidney tissues and significantly upregulated the expression of S100a8 and S100a9. S100a9 deletion downregulated S100a8 expression, decreased CD11b⁺Ly6c^high macrophages, and suppressed proinflammatory cytokine production in the kidney, attenuating LPS or ischemia reperfusion-induced renal inflammation and AKI. Bone marrow transplantation from S100a9^-/- mice donors, but not from wild-type mice donors, reduced infiltration of CD11b⁺Ly6c^high macrophages and renal inflammatory injury. S100a8/a9 overexpression activated the nuclear factor-κB signaling pathway and promoted the production of proinflammatory cytokines in macrophages.</p><p><strong>Conclusions: </strong>S100a8/a9 plays a regulatory role in CD11b⁺Ly6c^high macrophage population differentiation, contributing to endotoxemia-induced AKI. S100a8/a9 blockade may be a novel therapeutic strategy for the prevention or attenuation of AKI.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher Correction: Toxoplasma gondii infection reduces CD59 expression through downregulation of JAK2/STAT3 signaling axis to enhance decidual NK cell cytotoxicity via the RAS/MAPK pathway.","authors":"Shuyan Wang, Luyun Huo, Yan Zou, Ruohan Yang, Xiao Wang, Haixia Zhang, Liqin Ren, Jing Yang, Jie Li, Xuemei Hu, Yushan Ren","doi":"10.1007/s00011-026-02372-w","DOIUrl":"https://doi.org/10.1007/s00011-026-02372-w","url":null,"abstract":"","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR/Cas9-based nanodelivery systems for precision gene editing in neuroinflammation.","authors":"Sanjana Sahu, Parag Jain, Karan Kumar Dharme, Krishna Yadav","doi":"10.1007/s00011-026-02383-7","DOIUrl":"10.1007/s00011-026-02383-7","url":null,"abstract":"<p><strong>Background: </strong>Neuroinflammation is a characteristic feature of many neurological diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Uncontrolled activation of microglia and astrocytes results in the production of proinflammatory mediators that contribute to neuronal dysfunction and degeneration.</p><p><strong>Purpose: </strong>CRISPR/Cas9 genome-editing technology provides highly precise targeting of genes involved in these pathways, enabling the deletion, correction, or modulation of disease-associated genetic alterations. Nonetheless, effective delivery of CRISPR components to the central nervous system (CNS) remains a major challenge because of protective barriers such as the blood-brain barrier (BBB), as well as concerns regarding genomic instability and immunogenicity.</p><p><strong>Methods: </strong>Nanotechnology-guided delivery platforms, such as lipid nanoparticles, liposomes, dendrimers and polymeric carriers, have been developed as promising strategies to address these challenges. These nanosystems can improve biodistribution, pharmacokinetic behavior, and cellular uptake, while potentially reducing off-target effects and systemic toxicity.</p><p><strong>Results: </strong>The preclinical studies demonstrate successful modulation of key neuroinflammatory targets, including the NLRP3 inflammasome, triggering receptor expressed on myeloid cells 2 (TREM2), Janus kinase (JAK) signaling, and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, with potential therapeutic relevance to neurodegenerative diseases. In addition, novel techniques, such as mitochondrial base editing, prime editing, and epigenetic modulation, expand the scope of CRISPR-mediated therapeutic strategies. Although outcomes from animal models are promising, translation to the clinical setting requires careful consideration of safety, ethical concerns, and long-term efficacy.</p><p><strong>Conclusions: </strong>This review highlights the potential of integrating CRISPR/Cas9 with nanodelivery systems to advance precision medicine for neuroinflammatory disorders, while emphasizing their potential for therapeutic applications in complex CNS conditions. Ongoing studies aimed at optimizing delivery and reducing off-target effects will be essential for advancing these approaches toward clinical practice.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"75 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}