ReviewThe European journal of neuroscience2019
The unlikely partnership between LRRK2 and α-synuclein in Parkinson's disease.
Review in The European journal of neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- Discovery of multitargeting single agents as a novel route to the potential treatment of neurodegenerative diseases.Bioorganic & medicinal chemistry letters · 2026Article
- Longitudinal decline in striatal DAT binding in LRRK2 Parkinson's disease: connections with CSF α-synuclein seeding activity.Journal of neurology · 2025Article
- BetaBiomedicines · 2024Article
- Misfolded alpha-synuclein in amyotrophic lateral sclerosis: Implications for diagnosis and treatment.European journal of neurology · 2024Article
- Emerging perspectives on precision therapy for Parkinson's disease: multidimensional evidence leading to a new breakthrough in personalized medicine.Frontiers in aging neuroscience · 2024Review
- Leucine-rich repeat kinase 2 at a glance.Journal of cell science · 2023Article
- A leucine-rich repeat kinase 2 (LRRK2) pathway biomarker characterization study in patients with Parkinson's disease with and without LRRK2 mutations and healthy controls.Clinical and translational science · 2023Article
- Neuroprotective Effect of Melatonin on Sleep Disorders Associated with Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Long-term inhibition of mutant LRRK2 hyper-kinase activity reduced mouse brain α-synuclein oligomers without adverse effects.NPJ Parkinson's disease · 2022Article
- LRRK2 and Proteostasis in Parkinson's Disease.International journal of molecular sciences · 2022Review
- Differential Phospho-Signatures in Blood Cells Identify LRRK2 G2019S Carriers in Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- The Double-Faceted Role of Leucine-Rich Repeat Kinase 2 in the Immunopathogenesis of Parkinson's Disease.Frontiers in aging neuroscience · 2022Review
- Studying the effect of alpha-synuclein and Parkinson's disease linked mutants on inter pathway connectivities.Scientific reports · 2021Article
- Role of JAK/STAT in the Neuroinflammation and its Association with Neurological Disorders.Annals of neurosciences · 2021Review
- The C-Terminal Domain of LRRK2 with the G2019S Substitution Increases Mutant A53T α-Synuclein Toxicity in Dopaminergic Neurons In Vivo.International journal of molecular sciences · 2021Article
- Oligomerization of Lrrk controls actin severing and α-synuclein neurotoxicity in vivo.Molecular neurodegeneration · 2021Article
- Genes Implicated in Familial Parkinson's Disease Provide a Dual Picture of Nigral Dopaminergic Neurodegeneration with Mitochondria Taking Center Stage.International journal of molecular sciences · 2021Review
- Novel targeted therapies for Parkinson's disease.Molecular medicine (Cambridge, Mass.) · 2021Review
- Modulation of the Interactions Between α-Synuclein and Lipid Membranes by Post-translational Modifications.Frontiers in neurology · 2021Review
- LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies.Science translational medicine · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Our understanding of the mechanisms underlying Parkinson's disease, the once archetypical nongenetic neurogenerative disorder, has dramatically increased with the identification of α-synuclein and LRRK2 pathogenic mutations. While α-synuclein protein composes the aggregates that can spread through much of the brain in disease, LRRK2 encodes a multidomain dual-enzyme distinct from any other protein linked to neurodegeneration. In this review, we discuss emergent datasets from multiple model systems that suggest these unlikely partners do interact in important ways in disease, both within cells that express both LRRK2 and α-synuclein as well as through more indirect pathways that might involve neuroinflammation. Although the link between LRRK2 and disease can be understood in part through LRRK2 kinase activity (phosphotransferase activity), α-synuclein toxicity is multilayered and plausibly interacts with LRRK2 kinase activity in several ways. We discuss common protein interactors like 14-3-3s that may regulate α-synuclein and LRRK2 in disease. Finally, we examine cellular pathways and outcomes common to both mutant α-synuclein expression and LRRK2 activity and points of intersection. Understanding the interplay between these two unlikely partners in disease may provide new therapeutic avenues for 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.