ReviewNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2014
Heterogeneity of leucine-rich repeat kinase 2 mutations: genetics, mechanisms and therapeutic implications.
Review in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Recent advances in targeting LRRK2 for Parkinson's disease treatment.Journal of translational medicine · 2025Review
- The function of Golgi apparatus in LRRK2-associated Parkinson's disease.Frontiers in molecular neuroscience · 2023Review
- Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome.Biomolecules · 2022Review
- Pharmacological rescue of impaired mitophagy in Parkinson's disease-related LRRK2 G2019S knock-in mice.eLife · 2021Article
- The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease.Neurobiology of disease · 2021Article
- Development of a physiologically relevant and easily scalable LUHMES cell-based model of G2019S LRRK2-driven Parkinson's disease.Disease models & mechanisms · 2021Article
- Review
- The cell biology of Parkinson's disease.The Journal of cell biology · 2021Review
- Preclinical modeling of chronic inhibition of the Parkinson's disease associated kinase LRRK2 reveals altered function of the endolysosomal system in vivo.Molecular neurodegeneration · 2021Article
- Mitochondrial DNA damage as a potential biomarker of LRRK2 kinase activity in LRRK2 Parkinson's disease.Scientific reports · 2020Article
- Genetic variability and potential effects on clinical trial outcomes: perspectives in Parkinson's disease.Journal of medical genetics · 2020Article
- LRRK2 and the Endolysosomal System in Parkinson's Disease.Journal of Parkinson's disease · 2020Review
- Binding of the Human 14-3-3 Isoforms to Distinct Sites in the Leucine-Rich Repeat Kinase 2.Frontiers in neuroscience · 2020Article
- LRRK2 links genetic and sporadic Parkinson's disease.Biochemical Society transactions · 2019Review
- Crystal structure of the WD40 domain dimer of LRRK2.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Tied up: Does altering phosphoinositide-mediated membrane trafficking influence neurodegenerative disease phenotypes?Journal of genetics · 2018Review
- iPS cells in the study of PD molecular pathogenesis.Cell and tissue research · 2018Review
- Parkinson disease-associatedJournal of leukocyte biology · 2017Article
- LRRK2 Antisense Oligonucleotides Ameliorate α-Synuclein Inclusion Formation in a Parkinson's Disease Mouse Model.Molecular therapy. Nucleic acids · 2017Article
Corrections and comments
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2 authors.
Funding
Abstract
Variation within and around the leucine-rich repeat kinase 2 (LRRK2) gene is associated with familial and sporadic Parkinson's disease (PD). Here, we discuss the prevalence of LRRK2 substitutions in different populations and their association with PD, as well as molecular and cellular mechanisms of pathologically relevant LRRK2 mutations. Kinase activation was proposed as a universal molecular mechanism for all pathogenic LRRK2 mutations, but later reports revealed heterogeneity in the effect of mutations on different activities of LRRK2. One mutation (G2019S) increases kinase activity, whereas mutations in the Ras of complex proteins (ROC)-C-terminus of ROC (COR) bidomain impair the GTPase function of LRRK2. Some risk factor variants, including G2385R in the WD40 domain, actually decrease the kinase activity of LRRK2. We suggest a model where LRRK2 mutations exert different molecular mechanisms but interfere with normal cellular function of LRRK2 at different levels of the same downstream pathway. Finally, we discuss the current state of therapeutic approaches for LRRK2-related 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.