ArticleProceedings of the National Academy of Sciences of the United States of America2012
Roco kinase structures give insights into the mechanism of Parkinson disease-related leucine-rich-repeat kinase 2 mutations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 98 citations in OpenAlex.
- Regulation between LRRK2 and PP2A signaling in cellular models of Parkinson's disease.The Biochemical journal · 2026Article
- Discovery of Novel Chemotype LRRK2 Inhibitors Through AlphaFold2-Generated Structure-Based Docking Screen.International journal of molecular sciences · 2026Article
- Diverse Roles of the Multiple Phosphodiesterases in the Regulation of Cyclic Nucleotide Signaling inCells · 2025Review
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- LRRK2 Structure-Based Activation Mechanism and Pathogenesis.Biomolecules · 2023Review
- Review
- Structural Biology of LRRK2 and its Interaction with Microtubules.Movement disorders : official journal of the Movement Disorder Society · 2021Review
- Pathways to Parkinson's disease: a spotlight on 14-3-3 proteins.NPJ Parkinson's disease · 2021Review
- Markov State Models and Molecular Dynamics Simulations Provide Understanding of the Nucleotide-Dependent Dimerization-Based Activation of LRRK2 ROC Domain.Molecules (Basel, Switzerland) · 2021Article
- From structure to ætiology: a new window on the biology of leucine-rich repeat kinase 2 and Parkinson's disease.The Biochemical journal · 2021Article
- LRRK2 Targeting Strategies as Potential Treatment of Parkinson's Disease.Biomolecules · 2021Review
- Article
- Identification of LRRK2 missense variants in the accelerating medicines partnership Parkinson's disease cohort.Human molecular genetics · 2021Article
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
- Chemical IN04 Inhibits the Kinase Domain not the ROC Domain of LRRK1: Results from Homology Modeling and Molecular Docking.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2021Article
- A Conserved Role for LRRK2 and Roco Proteins in the Regulation of Mitochondrial Activity.Frontiers in cell and developmental biology · 2021Article
- LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies.Science translational medicine · 2020Article
- Article
- Cell Motility and Cancer.Cancers · 2020Review
- Kinase Domain Is a Dynamic Hub for Driving LRRK2 Allostery.Frontiers in molecular neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson disease. Here we show that Dictyostelium discoideum Roco4 is a suitable model to study the structural and biochemical characteristics of the LRRK2 kinase and can be used for optimization of current and identification of new LRRK2 inhibitors. We have solved the structure of Roco4 kinase wild-type, Parkinson disease-related mutants G1179S and L1180T (G2019S and I2020T in LRRK2) and the structure of Roco4 kinase in complex with the LRRK2 inhibitor H1152. Taken together, our data give important insight in the LRRK2 activation mechanism and, most importantly, explain the G2019S-related increase in LRRK2 kinase activity.
Indexed as
Identifiers
What OpenQuestion holds
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.