ArticleActa neuropathologica2023
Mutant LRRK2 exacerbates immune response and neurodegeneration in a chronic model of experimental colitis.
Article in Acta neuropathologica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 31 citations in OpenAlex.
- The Parkinson's disease-linked G2019S mutation of LRRK2 increases NADPH oxidase-2 activity in neutrophils for superior control of bacterial infections.Cellular & molecular immunology · 2026Article
- Neuroinflammatory and Motor Alterations in LRRK2*G2019S Transgenic Mice Without Enhanced Vulnerability to Aging or Chronic MPTP-Induced Nigrostriatal Neurodegeneration.Journal of neurochemistry · 2026Article
- Amelioration of colitis through restored gut ecology using Christensenella intestinihominis AF73-05CM02 as a probiotic in mice.Communications biology · 2026Article
- miR-369-3p Modulates LRRK2-Mediated Inflammation and Autophagy in RAW264.7 Macrophages.International journal of molecular sciences · 2026Article
- Tissue-specific transcriptional epistasis between Prkn and Lrrk2 during mycobacterial infection.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice.Molecular neurodegeneration · 2026Article
- The role of gut dysbiosis in Parkinson's disease: pathophysiology, epidemiology, and emerging therapeutic strategies.Metabolic brain disease · 2026Review
- LRRK2NPJ Parkinson's disease · 2026Article
- Unveiling Shared Genetic Architectures and Causality: Intestinal Diseases and Neurological Diseases.Brain and behavior · 2026Article
- Inflammatory signaling differentially changes chromatin accessibility and gene expression of the PD- associated kinase LRRK2 between human and mice.bioRxiv : the preprint server for biology · 2026Article
- Intestinal inflammation promotes neuroinflammation and PD-associated nigrostriatal pathology independently of LRRK2 G2019S kinase activity.Frontiers in cellular neuroscience · 2026Article
- The G2019S LRRK2 mutation exacerbates α-synuclein and tau neuropathology through divergent pathways in Parkinson's disease models.Acta neuropathologica · 2025Article
- Assessing prevalence and risk factors for REM sleep behavior disorder among patients with inflammatory bowel disease.NPJ Parkinson's disease · 2025Article
- Targeting specific kinase substrates rescues increased colitis severity induced by the Crohn's disease-linked LRRK2-N2081D variant.The Journal of clinical investigation · 2025Article
- Gut Permeability and Microbiota in Parkinson's Disease: Mechanistic Insights and Experimental Therapeutic Strategies.International journal of molecular sciences · 2025Review
- Lrrk2 G2019S mutation incites increased cell-intrinsic neutrophil effector functions and intestinal inflammation in a model of infectious colitis.NPJ Parkinson's disease · 2025Article
- The interrelationship between intestinal immune cells and enteric α-synuclein in the progression of Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Review
- Abundant non-inclusion α-synuclein pathology in Lewy body-negative LRRK2-mutant cases.Acta neuropathologica · 2025Article
- The dual nature of neuroinflammation in networked brain.Frontiers in immunology · 2025Review
- Mild Chronic Colitis Exacerbates Intracerebral Inflammation in Mice with Parkinson's Disease Through LRRK2-Mediated Regulation of NF-κB Activation and Inhibition of Nrf2.Journal of inflammation research · 2025Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
The link between the gut and the brain in Parkinson's disease (PD) pathogenesis is currently a subject of intense research. Indeed, gastrointestinal dysfunction is known as an early symptom in PD and inflammatory bowel disease (IBD) has recently been recognised as a risk factor for PD. The leucine-rich repeat kinase 2 (LRRK2) is a PD- and IBD-related protein with highest expression in immune cells. In this study, we provide evidence for a central role of LRRK2 in gut inflammation and PD. The presence of the gain-of-function G2019S mutation significantly increases the disease phenotype and inflammatory response in a mouse model of experimental colitis based on chronic dextran sulphate sodium (DSS) administration. Bone marrow transplantation of wild-type cells into G2019S knock-in mice fully rescued this exacerbated response, proving the key role of mutant LRRK2 in immune cells in this experimental colitis model. Furthermore, partial pharmacological inhibition of LRRK2 kinase activity also reduced the colitis phenotype and inflammation. Moreover, chronic experimental colitis also induced neuroinflammation and infiltration of peripheral immune cells into the brain of G2019S knock-in mice. Finally, combination of experimental colitis with overexpression of α-synuclein in the substantia nigra aggravated motor deficits and dopaminergic neurodegeneration in G2019S knock-in mice. Taken together, our results link LRRK2 with the immune response in colitis and provide evidence that gut inflammation can impact brain homeostasis and contribute to neurodegeneration in PD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.