ArticleHuman molecular genetics2012
LRRK2 Parkinson disease mutations enhance its microtubule association.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
118 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- The association between the LRRK2 G2385R variant and the risk of Parkinson's disease: a meta-analysis based on 23 case-control studies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2014Pooled it
- Article
- Parkinson's disease-associated LRRK2 risk variant, G2385R, enhances Rab substrate phosphorylation and impairs neuronal integrity.Human molecular genetics · 2026Article
- Article
- The structural basis for LRRK2's activation and autoinhibition.bioRxiv : the preprint server for biology · 2026Article
- Role of LRRK2 in physiological activities, diseases, and therapy.Chinese medical journal · 2026Review
- Article
- Mitochondrial organization in the developing proximal tubule is controlled by LRRK2.Nature communications · 2025Article
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Structural biology of Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2).The Journal of biological chemistry · 2025Review
- Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2.bioRxiv : the preprint server for biology · 2025Article
- Role of LRRK2 in axonal transport and Parkinson's disease.The Biochemical journal · 2025Review
- Type II kinase inhibitors that target Parkinson's disease-associated LRRK2.Science advances · 2025Article
- Genetic evidence for a functional association between Parkinson's disease proteins leucine-rich repeat kinase 2 andFrontiers in molecular neuroscience · 2025Article
- A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.The Journal of biological chemistry · 2024Article
- RedOx regulation of LRRK2 kinase activity by active site cysteines.NPJ Parkinson's disease · 2024Article
- Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?Antioxidants (Basel, Switzerland) · 2024Review
- Blocking IL-6 signaling prevents astrocyte-induced neurodegeneration in an iPSC-based model of Parkinson's disease.JCI insight · 2024Article
- Inhibition of Parkinson's disease-related LRRK2 by type I and type II kinase inhibitors: Activity and structures.Science advances · 2023Article
- Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Dominant missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic causes of Parkinson disease (PD) and genome-wide association studies identify LRRK2 sequence variants as risk factors for sporadic PD. Intact kinase function appears critical for the toxicity of LRRK2 PD mutants, yet our understanding of how LRRK2 causes neurodegeneration remains limited. We find that most LRRK2 PD mutants abnormally enhance LRRK2 oligomerization, causing it to form filamentous structures in transfections of cell lines or primary neuronal cultures. Strikingly, ultrastructural analyses, including immuno-electron microscopy and electron microscopic tomography, demonstrate that these filaments consist of LRRK2 recruited onto part of the cellular microtubule network in a well-ordered, periodic fashion. Like LRRK2-related neurodegeneration, microtubule association requires intact kinase function and the WD40 domain, potentially linking microtubule binding and neurodegeneration. Our observations identify a novel effect of LRRK2 PD mutations and highlight a potential role for microtubules in the pathogenesis of LRRK2-related neurodegeneration.
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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.