Disease Models & Mechanisms最新文献_第5页

Transdifferentiated BLaER1 cells as a genetically tractable model to study the interaction of pathogenic fungi with macrophages. 转分化BLaER1细胞作为研究病原真菌与巨噬细胞相互作用的遗传可处理模型。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-08-05 DOI: 10.1242/dmm.052865

Johannes Sonnberger, Erik Böhm, Janik Adriana Tomás-Morales, Theresa Lange, Katrin Bagola, Lisa Denner, Lydia Kasper, Sascha Brunke, Ger van Zandbergen, Jakob L Sprague, Bernhard Hube

{"title":"Transdifferentiated BLaER1 cells as a genetically tractable model to study the interaction of pathogenic fungi with macrophages.","authors":"Johannes Sonnberger, Erik Böhm, Janik Adriana Tomás-Morales, Theresa Lange, Katrin Bagola, Lisa Denner, Lydia Kasper, Sascha Brunke, Ger van Zandbergen, Jakob L Sprague, Bernhard Hube","doi":"10.1242/dmm.052865","DOIUrl":"10.1242/dmm.052865","url":null,"abstract":"Macrophages are essential in the defense against fungal disease. Elucidating antimicrobial mechanisms of macrophages and pathogen activities to evade these phagocytes will help in understanding fungal infections. Existing experimental models, however, have a number of disadvantages. Human macrophage-like cell lines offer genetic tractability, but often display reduced antifungal activity and altered phenotypes compared to primary cells. In contrast, primary human monocyte-derived macrophages closely reflect physiological responses but their use is constrained by donor variability, limited availability and restricted genetic manipulability. Here, we establish transdifferentiated BLaER1 cells as a human-derived, highly potent and genetically tractable infection model to study fungal-host interactions. We show that BLaER1 cells display macrophage characteristics and rapidly phagocytose cells of the major fungal pathogens Candida albicans, C. glabrata and C. auris. BLaER1 cells form functional phagolysosomes and elicit pro-inflammatory immune responses. Using knockout BLaER1 cells, we demonstrate for the first time in a human macrophage model that the host factor gasdermin D and the fungal peptide toxin candidalysin have distinct roles in triggering pyroptosis and inducing lytic host cell death.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249547","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}

引用次数: 0

Organoids as brain tumour models: bridging the translational gap. 类器官作为脑肿瘤模型：弥合翻译差距。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-09-01 DOI: 10.1242/dmm.052893

Thomas Willott, Silvia Marino

引用次数: 0

Expanding the scope of Mycobacterium abscessus reference strains to improve pulmonary disease modeling. 扩大脓肿分枝杆菌参考菌株范围以改进肺部疾病建模。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-09-01 DOI: 10.1242/dmm.052759

Ruth A Howe, Chavis Tabor, Chandra M Panthi, Guoqing Cheng, Binayak Rimal, Evan Chen, Ngan Nguyen, Gyanu Lamichhane

{"title":"Expanding the scope of Mycobacterium abscessus reference strains to improve pulmonary disease modeling.","authors":"Ruth A Howe, Chavis Tabor, Chandra M Panthi, Guoqing Cheng, Binayak Rimal, Evan Chen, Ngan Nguyen, Gyanu Lamichhane","doi":"10.1242/dmm.052759","DOIUrl":"10.1242/dmm.052759","url":null,"abstract":"Mycobacterium abscessus (Mab) pulmonary disease is an emerging clinical challenge, particularly in individuals with immunosuppression or structural lung disease. No US Food and Drug Administration (FDA)-approved therapies exist, and current multidrug regimens are prolonged, toxic and achieve low cure rates, highlighting the need for improved treatments. Progress depends on preclinical models that faithfully recapitulate human disease, for which strain selection is critical. The widely used reference strain, ATCC 19977, was isolated from a non-pulmonary source but became the default owing to early availability. To assess its relevance for modeling pulmonary disease, we compared it with 15 clinical Mab isolates from lung infections across the United States. In vitro and in a validated mouse lung infection model, ATCC 19977 differed markedly from clinical isolates, exhibiting rapid systemic dissemination, limited lung granuloma formation and early mortality. In contrast, clinical isolates demonstrated greater pulmonary tropism, reduced dissemination and robust lung pathology. We propose a panel of pulmonary clinical isolates representing major Mab subspecies and phenotypes for lung research. These isolates more accurately recapitulate human disease and are expected to enhance the translational relevance of mechanistic and therapeutic studies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864002","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}

引用次数: 0

Four new mouse models of Duchenne muscular dystrophy with clinically relevant exon deletions in the human DMD gene. 人类DMD基因临床相关外显子缺失的四种新的杜氏肌营养不良小鼠模型。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-08-28 DOI: 10.1242/dmm.052875

Maaike van Putten, Margot Linssen, Christa Tanganyika-de Winter, Conny M Brouwers, Jill W C Claassens, Nisha Verwey, Max Walsh, Tiberiu Loredan Stan, Annemieke Aartsma-Rus, Peter Hohenstein

{"title":"Four new mouse models of Duchenne muscular dystrophy with clinically relevant exon deletions in the human DMD gene.","authors":"Maaike van Putten, Margot Linssen, Christa Tanganyika-de Winter, Conny M Brouwers, Jill W C Claassens, Nisha Verwey, Max Walsh, Tiberiu Loredan Stan, Annemieke Aartsma-Rus, Peter Hohenstein","doi":"10.1242/dmm.052875","DOIUrl":"10.1242/dmm.052875","url":null,"abstract":"Variant-specific therapeutic approaches, such as exon skipping or gene editing, hold promise for the treatment of Duchenne muscular dystrophy (DMD). Translatability of preclinical studies investigating these approaches could greatly be improved through the use of humanized mouse models, as these allow preclinical testing of human-specific sequences. We developed four novel humanized mouse models of DMD with a deletion of exon 44, 45, 51 or 53 in the human DMD gene, in a mouse dystrophin-negative background (mdx mouse; exon 23 nonsense mutation). Our optimized prescreening pipeline allowed us to do so very efficiently with the CRISPR-Cas9 technology. We confirmed either complete lack of dystrophin or expression of trace levels, which led to development of muscle pathology consisting of muscle fiber degeneration and regeneration, inflammation and fibrosis in young adult mice. Intramuscular treatment with vivo-morpholinos targeting a flanking exon induced exon skipping in the DMD strains, which restored the disrupted open reading frame and, subsequently, dystrophin expression. This validates these models as valuable tools for preclinical studies investigating human sequence-specific therapeutic approaches for DMD.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789441","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}

引用次数: 0

The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology. 指导性瘢痕——细胞外基质在胆道病理生理中的动态作用。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-08-24 DOI: 10.1242/dmm.052835

Scott H Waddell, Euan Brennan, Luke Boulter

{"title":"The instructive scar - the dynamic role of extracellular matrix in biliary pathophysiology.","authors":"Scott H Waddell, Euan Brennan, Luke Boulter","doi":"10.1242/dmm.052835","DOIUrl":"10.1242/dmm.052835","url":null,"abstract":"Cholangiopathies - congenital and acquired diseases of the hepatic bile ducts within the liver - are often considered rare pathologies but contribute to a significant proportion of all liver transplantations. Cholangiopathies present a challenge in the clinic, often due to a lack of targeted, specific therapies, thereby underscoring the need for the development of new treatments. As with many chronic diseases, cholangiopathies exist as a spectrum; they are associated with increased inflammation and fibrosis throughout disease progression that, ultimately, result in reduced liver function and increased likelihood of developing biliary tract cancers (cholangiocarcinoma). Fibrotic scarring surrounding diseased bile ducts is characterised by aberrant changes to the molecular composition of the extracellular matrix. The contribution of individual cell types to the deposition and remodelling of the extracellular matrix, as well as its molecular composition, varies between cholangiopathies. Although a broad-strokes characterisation of the extracellular matrix is well established, how it conveys biochemical and biomechanical signals to the biliary epithelial cells (cholangiocytes) and how these interactions inform ductular cells to coordinate tissue-level regeneration and underpin the molecular pathology of the cholangiopathies is not well understood. In this Review, we explore the mechanisms and roles of an altered extracellular matrix in cholangiopathies and discuss the current and future perspectives for therapeutic strategies for targeting these processes in the clinic to intervene in cholangiopathies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808495","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}

引用次数: 0

Survivin drives renal cell carcinoma tumorigenesis via proliferative and metabolic adaptation. Survivin通过增殖和代谢适应驱动肾细胞癌的发生。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-08-25 DOI: 10.1242/dmm.052706

Shivani Tuli, Gabrielle Inserra, Yamato Murakami, Cais Vo, Sarvesh Senguttavan, Yongho Bae, Dave Gau

{"title":"Survivin drives renal cell carcinoma tumorigenesis via proliferative and metabolic adaptation.","authors":"Shivani Tuli, Gabrielle Inserra, Yamato Murakami, Cais Vo, Sarvesh Senguttavan, Yongho Bae, Dave Gau","doi":"10.1242/dmm.052706","DOIUrl":"10.1242/dmm.052706","url":null,"abstract":"Renal cell carcinoma (RCC) is a heterogeneous malignancy for which clear cell RCC (ccRCC) represents the most common and clinically aggressive subtype. Survivin (encoded by BIRC5), an inhibitor of apoptosis and key regulator of mitosis, is frequently overexpressed in RCC and associated with poor prognosis, yet its broader role in kidney cancer biology remains poorly defined. By analyzing transcriptomic data from The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC) cohort, we found that advanced-stage ccRCC exhibits widespread dysregulation of cell-cycle pathways, with 15,160 genes upregulated and 479 genes downregulated in stage IV compared to stage I tumors. To define survivin's functional contribution, we performed loss-of-function and pharmacologic inhibition studies in murine RENCA and human 786-O RCC cell lines. Survivin knockdown or treatment with the small-molecule inhibitor YM155 reduced proliferation, S-phase entry and cyclin D1 expression, and impaired collective (wound-healing), single-cell and transwell migration. Unexpectedly, survivin depletion increased mitochondrial content while lowering oxygen consumption, indicating accumulation of dysfunctional mitochondria. Together, these findings identify survivin as a node between cell-cycle progression and mitochondria in RCC.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812136","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}

引用次数: 0

Co-mutations of CTNNB1 and PTEN drive aggressive tumor progression in endometrial cancer. CTNNB1和PTEN的共同突变驱动子宫内膜癌的侵袭性肿瘤进展。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-07-01 Epub Date: 2026-06-18 DOI: 10.1242/dmm.052788

Shamsun Nahar, Eunhee M Jeong, Keun Cheon Kim, Russell Broaddus, Jung-Yoon Yoo, Jae-Wook Jeong, Kyeong A So, Tae Hoon Kim

{"title":"Co-mutations of CTNNB1 and PTEN drive aggressive tumor progression in endometrial cancer.","authors":"Shamsun Nahar, Eunhee M Jeong, Keun Cheon Kim, Russell Broaddus, Jung-Yoon Yoo, Jae-Wook Jeong, Kyeong A So, Tae Hoon Kim","doi":"10.1242/dmm.052788","DOIUrl":"10.1242/dmm.052788","url":null,"abstract":"Endometrioid endometrial cancer (EEC) is the most prevalent gynecological malignancy. While early-stage EEC typically carries a favorable prognosis, late-stage EEC shows significantly poorer outcomes, with a five-year survival rate of only 17-19%. Co-occurring PTEN and CTNNB1 variants are frequent in EEC and linked to poor prognosis. To investigate their functional impact, we generated uterine-specific Pten knockout mice and dominantly stabilized Ctnnb1 mutant mice (Pgrcre/+Ptenf/fCtnnb1f(ex3)/+; Ptend/dCtnnb1f(ex3)/+). These double-mutant mice exhibited significantly reduced survival compared to single Pten knockout (Pgrcre/+Ptenf/f; Ptend/d) mice. Histopathology revealed aggressive, metastatic endometrioid cancer in Ptend/dCtnnb1f(ex3)/+ mice; these mice developed myometrial invasion by four weeks of age - unlike Ptend/d mice. Transcriptomic analysis identified activation of multiple oncogenic pathways, including WNT/CTNNB1, PI3K/AKT, basal cell carcinoma, sonic hedgehog signaling and epithelial-mesenchymal transition (EMT). Immunohistochemistry confirmed hallmark features of EMT in the uterus of double-mutant mice, including strong downregulation of E-cadherin (CDH1) and upregulation of the EMT regulator SNAIL (Snai1). These findings demonstrate that synergistic mutations of PTEN and CTNNB1 promote early invasion, EMT activation, and metastatic progression, offering mechanistic insight into the aggressive behavior and poor clinical outcomes associated with this subtype of EEC.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13312928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270634","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}

引用次数: 0

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-07-01 Epub Date: 2026-07-24 DOI: 10.1242/dmm.052957

David A Hume, Katharine M Irvine

{"title":"CSF1R-related leukoencephalopathy: experimental models and potential for treatment.","authors":"David A Hume, Katharine M Irvine","doi":"10.1242/dmm.052957","DOIUrl":"10.1242/dmm.052957","url":null,"abstract":"Dominant and recessive mutations in the human CSF1R gene are associated with microglial deficiency in the brain and severe neurodegenerative disease, known as CSF1R-related leukoencephalopathy (CRL). Dominant and recessive Csf1r mutations have been generated in mice, rats, zebrafish and chicken, providing models of the complete or partial microglial loss seen in patients. The impact of Csf1r mutations in inbred mice depends upon genetic background. For example, Csf1r mutants in the C57BL/6J strain are uniquely susceptible to perinatal mortality and hydrocephalus. Congenital microglial deficiency in a range of animal models does not influence postnatal brain development but is associated with age-dependent neuropathology that resembles CRL, indicating that microglial deficiency contributes to disease. None of the available models fully recapitulates the severe functional motor and cognitive impairments seen in patients, raising questions about species differences and the relative contributions of genetic and environmental modifiers. However, they have provided platforms to test ways to repopulate the brain with functional microglia. Here, we briefly review the genetic basis for CRL and evidence of variable penetrance. We also assess experimental models that can enable the development of therapeutic strategies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 7","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577533","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}

引用次数: 0

Multiple mechanisms lead to loss-of-function effects of pathogenic SARS2 variants. 多种机制导致SARS2变异的功能丧失效应：基因型-表型分析的意义

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-07-01 Epub Date: 2026-07-24 DOI: 10.1242/dmm.052690

Christina Del Greco, Stephanie M Laureano Figueroa, Anthony Antonellis

{"title":"Multiple mechanisms lead to loss-of-function effects of pathogenic SARS2 variants.","authors":"Christina Del Greco, Stephanie M Laureano Figueroa, Anthony Antonellis","doi":"10.1242/dmm.052690","DOIUrl":"10.1242/dmm.052690","url":null,"abstract":"Seryl-tRNA synthetase 2 (SARS2) encodes the enzyme responsible for charging tRNA with serine in the mitochondria. SARS2 has been associated with a spectrum of recessive diseases including HUPRA syndrome and progressive spastic paresis. Previous studies showed that pathogenic SARS2 variants cause decreased tRNA charging; however, the mechanism by which specific variants lead to distinct recessive phenotypes has not been defined. To address this lack of knowledge, we studied an allelic series of 11 pathogenic SARS2 variants for differential effects on mitochondrial function. These efforts revealed compelling variant-dependent effects on oxygen consumption that will be useful for genotype-phenotype correlations. Interestingly, certain variants (including the most commonly detected pathogenic SARS2 variant, R402H) did not affect mitochondrial function in our model system. Computational and functional studies revealed that two missense variants in exon 13 (D390G and R402H) reduce exon inclusion, suggesting loss-of-function effects via impaired transcript processing. Overall, this study expands our understanding of SARS2 biology, reveals differential effects that pathogenic variants have on SARS2 function, and provides the foundation for defining the clinical heterogeneity of patient phenotypes.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136779","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}

引用次数: 0

Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis. Fos调节VAPBALS的年龄依赖性神经炎症。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-07-01 Epub Date: 2026-07-24 DOI: 10.1242/dmm.052810

Namrata Pramod Kulkarni, Aparna Thulasidharan, Amarendranath Soory, Pulkit Goel, Sanhita Sarkar, Vidyadheesh Kelkar, Girish S Ratnaparkhi

{"title":"Fos regulates age-dependent neuroinflammation in a VAPP58S model of amyotrophic lateral sclerosis.","authors":"Namrata Pramod Kulkarni, Aparna Thulasidharan, Amarendranath Soory, Pulkit Goel, Sanhita Sarkar, Vidyadheesh Kelkar, Girish S Ratnaparkhi","doi":"10.1242/dmm.052810","DOIUrl":"10.1242/dmm.052810","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive loss of motor function. Here, we developed a Drosophila model of ALS8 (VAPBP58S) using CRISPR/Cas9 genome editing. VAPB is an endoplasmic reticulum-based adapter protein associated with and regulating intracellular membrane:membrane contact sites. VAPBP58S flies showed progressive age-dependent motor deficits and a shortened lifespan, paralleling features of the human disease. VAPBP58S brains exhibited age-dependent neuroinflammation, as measured by whole-transcriptome quantitative mRNA sequencing, suggesting a broad, low-grade enhancement of signalling across multiple immune pathways (Toll, Imd, Jak-STAT and c-Jun). Our results indicated that glial cells in the brain are the site of brain inflammation and identified the Drosophila orthologue of Fos (Kayak) as a key modulator of age-dependent inflammation. In accordance, we found that overexpression of wild-type kayak or its dominant-active variant kayakK357R in glia reduced inflammation and, concomitantly, improved motor function. In contrast, knockdown of glial kayak accelerated age-dependent deterioration of motor function and enhanced neuroinflammation. Our study underscores the roles of glial-modulated brain inflammation in dictating ALS8 progression and identifies kayak as a central negative regulator of neuroinflammation in disease.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13446562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155723","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}

引用次数: 0