ArticleHuman molecular genetics2012
LRRK2 functions as a Wnt signaling scaffold, bridging cytosolic proteins and membrane-localized LRP6.
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 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Coding and Noncoding Variation in LRRK2 and Parkinson's Disease Risk.Movement disorders : official journal of the Movement Disorder Society · 2022Pooled it
- LRRK2 G2019S reprograms innate and adaptive immunity to drive context-dependent host defense outcomes.Frontiers in cellular neuroscience · 2026Article
- Cranial glucose metabolic patterns across prodromal and clinical parkinson's disease revealed byEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Excess Wnt in neurological disease.The Biochemical journal · 2025Review
- Adult ADHD as a risk factor for dementia: integrating longitudinal evidence, mechanistic insights, and the role of stimulant treatment.Frontiers in dementia · 2025Review
- Dysregulated Wnt and NFAT signaling in a Parkinson's disease LRRK2 G2019S knock-in model.Scientific reports · 2024Article
- How Parkinson's Disease-Linked LRRK2 Mutations Affect Different CNS Cell Types.Journal of Parkinson's disease · 2024Review
- Development of a highly potent and selective degrader of LRRK2.Bioorganic & medicinal chemistry letters · 2023Article
- Roc, the G-domain of the Parkinson's disease-associated protein LRRK2.Trends in biochemical sciences · 2022Review
- Review
- PSEN2 Thr421Met Mutation in a Patient with Early Onset Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Transcriptome Profiling of the Hippocampal Seizure Network Implicates a Role for Wnt Signaling during Epileptogenesis in a Mouse Model of Temporal Lobe Epilepsy.International journal of molecular sciences · 2022Article
- Article
- BRD2 interconnects with BRD3 to facilitate Pol II transcription initiation and elongation to prime promoters for cell differentiation.Cellular and molecular life sciences : CMLS · 2022Article
- Association Between Pathophysiological Mechanisms of Diabetic Retinopathy and Parkinson's Disease.Cellular and molecular neurobiology · 2022Review
- Midbrain organoids mimic early embryonic neurodevelopment and recapitulate LRRK2-p.Gly2019Ser-associated gene expression.American journal of human genetics · 2022Article
- Trophoblast glycoprotein is a new candidate gene for Parkinson's disease.NPJ Parkinson's disease · 2021Article
- Parkinson's in the bone.Cell & bioscience · 2021Review
- In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung.Brain research · 2021Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in PARK8, encoding leucine-rich repeat kinase 2 (LRRK2), are a frequent cause of Parkinson's disease (PD). Nonetheless, the physiological role of LRRK2 remains unclear. Here, we demonstrate that LRRK2 participates in canonical Wnt signaling as a scaffold. LRRK2 interacts with key Wnt signaling proteins of the β-catenin destruction complex and dishevelled proteins in vivo and is recruited to membranes following Wnt stimulation, where it binds to the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) in cellular models. LRRK2, therefore, bridges membrane and cytosolic components of Wnt signaling. Changes in LRRK2 expression affects pathway activity, while pathogenic LRRK2 mutants reduce both signal strength and the LRRK2-LRP6 interaction. Thus, decreased LRRK2-mediated Wnt signaling caused by reduced binding to LRP6 may underlie the neurodegeneration observed in PD. Finally, a newly developed LRRK2 kinase inhibitor disrupted Wnt signaling to a similar extent as pathogenic LRRK2 mutations. The use of LRRK2 kinase inhibition to treat PD may therefore need reconsideration.
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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.