Elevated Urinary Rab10 Phosphorylation in Idiopathic Parkinson Disease.

ABSTRACT:

Background

Pathogenic leucine-rich repeat kinase 2 LRRK2 mutations may increase LRRK2 kinase activity and Rab substrate phosphorylation. Genetic association studies link variation in LRRK2 to idiopathic Parkinson disease (iPD) risk.

Objectives

Through measurements of the LRRK2 kinase substrate pT73-Rab10 in urinary extracellular vesicles, this study seeks to understand how LRRK2 kinase activity might change with iPD progression.

Methods

Using an immunoblotting approach validated in LRRK2 transgenic mice, the ratio of pT73-Rab10 to total Rab10 protein was measured in extracellular vesicles from a cross-section of G2019S LRRK2 mutation carriers (N = 45 participants) as well as 485 urine samples from a novel longitudinal cohort of iPD and controls (N = 85 participants).

SUBMITTER: Wang S 

PROVIDER: S-EPMC9308673 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature