ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
LRRK2 Gly2019Ser Mutation Promotes ER Stress via Interacting with THBS1/TGF-β1 in Parkinson's Disease.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 32 citations in OpenAlex.
- Disrupted TFEB/GDNF-cAMP/ATP Coupling Underlies Astrocytic Dysfunction and Depression in LRRK2 G2019S Parkinson's Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Strategies for Optimizing Genetic Mouse Models to Enhance the Understanding of Parkinson's Disease.Biomedicines · 2026Review
- The Bright and Dark Sides of Nitric Oxide in Neurodegenerative Diseases.Journal of personalized medicine · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- LRRK2 I1371V Mutation Drives Astrocytic Glucose Metabolism Failure and Induces Integrated ER-Mitochondria-Lysosome Dysfunction in Parkinson's Disease.International journal of molecular sciences · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Spatiotemporal dynamics of reactive oxygen species: implications for cellular homeostasis and redox therapies.Cellular & molecular biology letters · 2026Review
- CGRP/TSP1 Signaling Dampens Corneal Inflammation and Fibrosis by Targeting A2M During Corneal Stromal Wound Healing.Investigative ophthalmology & visual science · 2026Article
- Multi-omics profiling identifies ADAM9 as a key efferocytosis driver in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Mitochondria-ER contact sites in neurological disorders.Animal cells and systems · 2026Review
- PACS-2 Mitigates NPSC Apoptosis and Intervertebral Disc Degeneration by Preserving MAM Integrity via the SP1/LRRK2/Mfn2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Obacunone Inhibits Microglia-Mediated Neuroinflammation and Ischemic Injury by Targeting Mitogen-Activated Protein Kinase 1.Journal of inflammation research · 2026Article
- LRRK2 Mediates α-Synuclein-Induced Neuroinflammation and Ferroptosis through the p62-Keap1-Nrf2 Pathway in Parkinson's Disease.Inflammation · 2025Article
- Regulation of LRRK2 activity by metabolic stress and heavy metal exposure.Brain research · 2025Article
- Interplay of α-Synuclein Oligomers and Endoplasmic Reticulum Stress in Parkinson'S Disease: Insights into Cellular Dysfunctions.Inflammation · 2025Review
- GPX3 promotes cisplatin resistance in TNBC by manipulating ROS-TGFB1-ZEB2.Cell communication and signaling : CCS · 2025Article
- Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway.The world journal of men's health · 2025Article
- The p.R321C mutation in the p62 protein is associated with abnormalities in the central nervous system.Scientific reports · 2025Article
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Authors and funding
8 authors at 4 institutions in 4 countries.
Funding
Abstract
The gene mutations of LRRK2, which encodes leucine-rich repeat kinase 2 (LRRK2), are associated with one of the most prevalent monogenic forms of Parkinson's disease (PD). However, the potential effectors of the Gly2019Ser (G2019S) mutation remain unknown. In this study, the authors investigate the effects of LRRK2 G2019S on endoplasmic reticulum (ER) stress in induced pluripotent stem cell (iPSC)-induced dopamine neurons and explore potential therapeutic targets in mice model. These findings demonstrate that LRRK2 G2019S significantly promotes ER stress in neurons and mice. Interestingly, inhibiting LRRK2 activity can ameliorate ER stress induced by the mutation. Moreover, LRRK2 mutation can induce ER stress by directly interacting with thrombospondin-1/transforming growth factor beta1 (THBS1/TGF-β1). Inhibition of LRRK2 kinase activity can effectively suppress ER stress and the expression of THBS1/TGF-β1. Knocking down THBS1 can rescue ER stress by interacting with TGF-β1 and behavior burden caused by the LRRK2 mutation, while suppression of TGF-β1 has a similar effect. Overall, it is demonstrated that the LRRK2 mutation promotes ER stress by directly interacting with THBS1/TGF-β1, leading to neural death in PD. These findings provide valuable insights into the pathogenesis of PD, highlighting potential diagnostic markers and therapeutic targets.
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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.