ArticlePloS one2009
The WD40 domain is required for LRRK2 neurotoxicity.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 108 citations in OpenAlex.
- Parkinson's disease-associated LRRK2 risk variant, G2385R, enhances Rab substrate phosphorylation and impairs neuronal integrity.Human molecular genetics · 2026Article
- Cell-autonomous role of leucine-rich repeat kinase in the protection of dopaminergic neuron survival.eLife · 2024Article
- Neuroprotective Effects of the Nutraceutical Dehydrozingerone and Its CBiomolecules · 2024Article
- Role of the leucine-rich repeat protein kinase 2 C-terminal tail in domain cross-talk.The Biochemical journal · 2024Article
- Regulation of LRRK2 mRNA stability by ATIC and its substrate AICAR through ARE-mediated mRNA decay in Parkinson's disease.The EMBO journal · 2023Article
- Pathophysiological evaluation of the LRRK2 G2385R risk variant for Parkinson's disease.NPJ Parkinson's disease · 2022Article
- Genetic variations inFrontiers in neurology · 2022Review
- LRRK2 Targeting Strategies as Potential Treatment of Parkinson's Disease.Biomolecules · 2021Review
- A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson's Disease Affects LRRK2 Protein Levels.International journal of molecular sciences · 2021Article
- Review
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
- Allosteric inhibition of LRRK2, where are we now.Biochemical Society transactions · 2020Review
- LRRK2 Phosphorylation, More Than an Epiphenomenon.Frontiers in neuroscience · 2020Review
- LRRK2 Biology from structure to dysfunction: research progresses, but the themes remain the same.Molecular neurodegeneration · 2019Review
- Differences in Stability, Activity and Mutation Effects Between Human and Mouse Leucine-Rich Repeat Kinase 2.Neurochemical research · 2019Article
- Crystal structure of the WD40 domain dimer of LRRK2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- LRRK2 and mitochondria: Recent advances and current views.Brain research · 2019Review
- Insights into the Influence of Specific Splicing Events on the Structural Organization ofInternational journal of molecular sciences · 2018Article
- Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins.Proteomics · 2018Article
- The LRRK2 Variant E193K Prevents Mitochondrial Fission Upon MPP+ Treatment by Altering LRRK2 Binding to DRP1.Frontiers in molecular neuroscience · 2018Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson disease (PD). LRRK2 contains an "enzymatic core" composed of GTPase and kinase domains that is flanked by leucine-rich repeat (LRR) and WD40 protein-protein interaction domains. While kinase activity and GTP-binding have both been implicated in LRRK2 neurotoxicity, the potential role of other LRRK2 domains has not been as extensively explored. PRINCIPAL
findingsWe demonstrate that LRRK2 normally exists in a dimeric complex, and that removing the WD40 domain prevents complex formation and autophosphorylation. Moreover, loss of the WD40 domain completely blocks the neurotoxicity of multiple LRRK2 PD mutations.
conclusionThese findings suggest that LRRK2 dimerization and autophosphorylation may be required for the neurotoxicity of LRRK2 PD mutations and highlight a potential role for the WD40 domain in the mechanism of LRRK2-mediated cell death.
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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.