ReviewSmall GTPases
Contribution of GTPase activity to LRRK2-associated Parkinson disease.
Review in Small GTPases. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Bridging the gap in Parkinson's disease research: from general pathophysiology to advanced 3d cell culture models.Cell communication and signaling : CCS · 2025Review
- Pathological and Therapeutic Advances in Parkinson's Disease: Mitochondria in the Interplay.Journal of Alzheimer's disease : JAD · 2023Review
- Modelling the functional genomics of Parkinson's disease in Caenorhabditis elegans: LRRK2 and beyond.Bioscience reports · 2021Review
- LRRK2 Targeting Strategies as Potential Treatment of Parkinson's Disease.Biomolecules · 2021Review
- Article
- Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease.Frontiers in neurology · 2021Article
- Chaperones and Proteostasis: Role in Parkinson's Disease.Diseases (Basel, Switzerland) · 2020Review
- Fluctuation Imaging of LRRK2 Reveals that the G2019S Mutation Alters Spatial and Membrane Dynamics.Molecules (Basel, Switzerland) · 2020Article
- Epigenetic mechanisms of neurodegenerative diseases and acute brain injury.Neurochemistry international · 2020Review
- Rab GTPases as Physiological Substrates of LRRK2 Kinase.Experimental neurobiology · 2019Review
- The Ras Superfamily of Small GTPases in Non-neoplastic Cerebral Diseases.Frontiers in molecular neuroscience · 2019Review
- LRRK2 kinase plays a critical role in manganese-induced inflammation and apoptosis in microglia.PloS one · 2019Article
- Insights into the Influence of Specific Splicing Events on the Structural Organization ofInternational journal of molecular sciences · 2018Article
- A new hypothesis for Parkinson's disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics.Molecular neurodegeneration · 2018Review
- The LRRK2 signalling system.Cell and tissue research · 2018Review
- A Novel Relationship for Schizophrenia, Bipolar, and Major Depressive Disorder. Part 8: a Hint from Chromosome 8 High Density Association Screen.Molecular neurobiology · 2017Article
- GTP binding regulates cellular localization of Parkinson's disease-associated LRRK2.Human molecular genetics · 2017Article
- Mechanisms of LRRK2-dependent neurodegeneration: role of enzymatic activity and protein aggregation.Biochemical Society transactions · 2017Review
- Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson's disease.Scientific reports · 2017Article
- Understanding the GTPase Activity of LRRK2: Regulation, Function, and Neurotoxicity.Advances in neurobiology · 2017Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 2 countries.
Funding
Abstract
Mutations in the leucine-rich repeat kinase 2 (LRRK2, PARK8, OMIM 607060) gene represent the most common known cause of hereditary Parkinson's disease (PD) with late-onset and dominant inheritance. LRRK2 protein is composed of multiple domains including two distinct enzymatic domains, a kinase and a Ras-of-complex (Roc) GTPase, connected by a C-terminal-of-Roc (COR) domain, and belongs to the ROCO protein family. Disease-causing mutations located in the kinase domain enhance kinase activity (i.e., G2019S) whereas mutations clustering within the Roc-COR tandem domain impair GTPase activity (i.e., R1441C/G and Y1699C). Familial LRRK2 mutations commonly induce neuronal toxicity that, at least for the frequent G2019S variant, is dependent on kinase activity. The contribution of GTPase activity to LRRK2-dependent neuronal toxicity is not yet clear. Therefore, both GTPase and kinase activity may be important for mediating neurodegeneration in PD due to familial LRRK2 mutations. At present, the physiological function of LRRK2 in the mammalian brain and the regulation of its enzymatic activity are incompletely understood. In this review, we focus on the GTPase domain of LRRK2 and discuss the recent advances in elucidating its function and its interplay with the kinase domain for the regulation of LRRK2 activity and toxicity. GTPase activity is an important feature of LRRK2 biology and pathophysiology and represents an underexplored yet potentially tractable therapeutic target for treating LRRK2-associated 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.