ArticleNPJ Parkinson's disease2020
Exosome markers of LRRK2 kinase inhibition.
Article in NPJ Parkinson's disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Photonic and nanomaterial-driven optical biosensing strategies for Parkinson's disease.Mikrochimica acta · 2026Review
- Parkinson's-Linked LRRK2 and GBA1 Mutations Modulate the Peripheral Immune Response to Pseudomonas aeruginosa.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Exosomes in Clinical Laboratory: From Biomarker Discovery to Diagnostic Implementation.Medicina (Kaunas, Lithuania) · 2025Review
- Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders.International journal of molecular sciences · 2025Review
- Single molecule array measures of LRRK2 kinase activity in serum link Parkinson's disease severity to peripheral inflammation.Molecular neurodegeneration · 2024Article
- A potential patient stratification biomarker for Parkinson´s disease based on LRRK2 kinase-mediated centrosomal alterations in peripheral blood-derived cells.NPJ Parkinson's disease · 2024Article
- Review
- LRRK2-Targeting Therapies March Through the Valley of Death.Movement disorders : official journal of the Movement Disorder Society · 2023Article
- Who to Enroll in Parkinson Disease Prevention Trials? The Case for Genetically At-Risk Cohorts.Neurology · 2022Review
- Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease.Movement disorders : official journal of the Movement Disorder Society · 2022Article
- Lysosomal dysfunction in neurodegeneration: emerging concepts and methods.Trends in neurosciences · 2022Review
- LRRK2 and idiopathic Parkinson's disease.Trends in neurosciences · 2022Review
- The role of extracellular vesicles in the physiological and pathological regulation of the blood-brain barrier.FASEB bioAdvances · 2021Review
- Extracellular Vesicles as Novel Diagnostic and Prognostic Biomarkers for Parkinson's Disease.Aging and disease · 2021Review
- Genetic background influences LRRK2-mediated Rab phosphorylation in the rat brain.Brain research · 2021Article
- Genetic and Environmental Factors Influence the Pleomorphy ofInternational journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyper-activated LRRK2 is linked to Parkinson's disease susceptibility and progression. Quantitative measures of LRRK2 inhibition, especially in the brain, maybe critical in the development of successful LRRK2-targeting therapeutics. In this study, two different brain-penetrant and selective LRRK2 small-molecule kinase inhibitors (PFE-360 and MLi2) were orally administered to groups of cynomolgus macaques. Proposed pharmacodynamic markers in exosomes from urine and cerebrospinal fluid (CSF) were compared to established markers in peripheral blood mononuclear cells (PBMCs). LRRK2 kinase inhibition led to reductions in exosome-LRRK2 protein and the LRRK2-substrate pT73-Rab10 in urine, as well as reduced exosome-LRRK2 and autophosphorylated pS1292-LRRK2 protein in CSF. We propose orthogonal markers for LRRK2 inhibition in urine and CSF can be used in combination with blood markers to non-invasively monitor the potency of LRRK2-targeting therapeutics.
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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.