ArticleNPJ Parkinson's disease2022
Mutant LRRK2 in lymphocytes regulates neurodegeneration via IL-6 in an inflammatory model of Parkinson's disease.
Article in NPJ Parkinson's disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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Who cites it
28 citing papers in PubMed, 37 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
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- Simulated wildfire smoke particulate matter elicits STING-dependent astrocyte-mediated inflammatory signaling and neurotoxicity.Neurotoxicology · 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
- Unraveling the intersection of aging and Parkinson's disease: a collaborative roadmap for advancing research models.NPJ Parkinson's disease · 2026Review
- 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
- Fractures in Parkinson's Disease: Pathophysiology, Prevention, and Orthopedic Outcomes.Cureus · 2025Review
- 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
- Environmental exposures and familial background alter the induction of neuropathology and inflammation after SARS-CoV-2 infection.NPJ Parkinson's disease · 2025Article
- Microbial Trojan Horses: Virulence Factors as Key Players in Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2025Review
- Exercise as a multitarget therapy: modulating myokines, neurotrophins, and inflammation in Parkinson's disease.Frontiers in aging neuroscience · 2025Review
- Variants in Lrrk2 and Snca deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice.PloS one · 2025Article
- TheScience translational medicine · 2024Article
- The Evolution of Genetic Variability at theGenes · 2024Article
- Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.Neurotoxicology · 2024Review
- Blocking IL-6 signaling prevents astrocyte-induced neurodegeneration in an iPSC-based model of Parkinson's disease.JCI insight · 2024Article
- What Can Inflammation Tell Us about Therapeutic Strategies for Parkinson's Disease?International journal of molecular sciences · 2024Review
- A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.NPJ Parkinson's disease · 2024Article
- The impact of interleukin-6 (IL-6) and mesenchymal stem cell-derived IL-6 on neurological conditions.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in a number of genes contribute to development of Parkinson's disease (PD), including several within the LRRK2 gene. However, little is known about the signals that underlie LRRK2-mediated neuronal loss. One clue resides in the finding that the neurodegenerative cascades emanate from signals arising from the peripheral immune system. Here, using two chimeric mouse models, we demonstrate that: 1) the replacement of mutant LRRK2 with wt form of the protein in T- and B-lymphocytes diminishes LPS-mediated inflammation and rescues the SNpc DA neuron loss in the mutant LRRK2 brain; 2) the presence of G2019S or R1441G LRRK2 mutation in lymphocytes alone is sufficient for LPS-induced DA neuron loss in the genotypically wt brain; and 3) neutralization of peripheral IL-6 overproduction prevents the SNpc DA neuron loss in LPS-treated mutant LRRK2 mice. These results represent a major paradigm shift in our understanding of PD pathogenesis and suggest that immune dysfunction in some forms of familial PD may have primacy over the CNS as the initiating site of the disorder.
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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.