{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T06:34:44Z","timestamp":1789454084595,"version":"build-2803163510"},"reference-count":91,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI155621"],"award-info":[{"award-number":["R01 AI155621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI145287"],"award-info":[{"award-number":["R01 AI145287"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"crossref","award":["PF-Launch-938138"],"award-info":[{"award-number":["PF-Launch-938138"]}],"id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mounting evidence supports a critical role for central nervous system (CNS) glial cells in neuroinflammation and neurodegenerative diseases, including Alzheimer\u2019s disease (AD), Parkinson\u2019s Disease (PD), Multiple Sclerosis (MS), as well as neurovascular ischemic stroke. Previously, we found that loss of the PD-associated gene leucine-rich repeat kinase 2 (Lrrk2) in macrophages, peripheral innate immune cells, induced mitochondrial stress and elevated basal expression of type I interferon (IFN) stimulated genes (ISGs) due to chronic mitochondrial DNA engagement with the cGAS\/STING DNA sensing pathway. Here we report that loss of LRRK2 results in a paradoxical response in microglial cells, a CNS-specific macrophage population. In primary murine microglia and microglial cell lines, loss of Lrrk2 reduces tonic IFN signaling leading to a reduction in ISG expression. Consistent with reduced type I IFN, mitochondria from Lrrk2 KO microglia are protected from stress and have elevated metabolism. These protective phenotypes involve upregulation of NRF2, an important transcription factor in the response to oxidative stress and are restricted by LRRK2 kinase activity. Collectively, these findings illustrate a dichotomous role for LRRK2 within different immune cell populations and give insight into the fundamental differences between immune regulation in the CNS and the periphery.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf215","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T18:35:46Z","timestamp":1757010946000},"source":"Crossref","is-referenced-by-count":7,"title":["LRRK2 kinase activity restricts NRF2-dependent mitochondrial protection in microglia"],"prefix":"10.1093","volume":"215","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8063-7794","authenticated-orcid":false,"given":"Chi G","family":"Weindel","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Texas A&M School of Medicine , Bryan, TX,","place":["United States"]},{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine , New Orleans, LA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aja K","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Texas A&M School of Medicine , Bryan, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lily M","family":"Ellzey","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine , New Orleans, LA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara L","family":"Chaisson","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine , New Orleans, LA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob R","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Texas A&M School of Medicine , Bryan, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2442-4679","authenticated-orcid":false,"given":"Kristin L","family":"Patrick","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Texas A&M School of Medicine , Bryan, TX,","place":["United States"]},{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4976-0759","authenticated-orcid":false,"given":"Robert O","family":"Watson","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Texas A&M School of Medicine , Bryan, TX,","place":["United States"]},{"name":"Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, TN,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"2026012707073310800_vkaf215-B1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.celrep.2016.12.041","article-title":"Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain","volume":"18","author":"Askew","year":"2017","journal-title":"Cell 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