Heterodimerization of Lrrk1-Lrrk2: Implications for LRRK2-associated Parkinson Disease

Overview

Journal Mech Ageing Dev

Specialty Geriatrics

Date 2010 Feb 11

PMID 20144646

Citations 10

Authors

Justus C Dachsel

Kenya Nishioka

Carles Vilarino-Guell

Sarah J Lincoln

Alexandra I Soto-Ortolaza

Jennifer Kachergus

Kelly M Hinkle

Michael G Heckman

Barbara Jasinska-Myga

Julie P Taylor

Dennis W Dickson

Rachel A Gibson

Faycal Hentati

Owen A Ross

Matthew J Farrer

Affiliations

Soon will be listed here.

Abstract

LRRK2 mutations are recognized as the most frequent genetic cause of both familial and sporadic parkinsonism identified to date. A remarkable feature of this form of parkinsonism is the variable penetrance of symptom manifestation resulting in a wide range of age-at-onset in patients. Herein we use a functional approach to identify the Lrrk1 protein as a potential disease modifier demonstrating an interaction and heterodimer formation with Lrrk2. In addition, evaluation of LRRK1 variants in our large Lrrk2 p.G2019S-parkinsonism series from a Tunisian (n=145) identified a missense mutation (p.L416M) resulting in an average 6.2 years younger age at disease onset. In conclusion we show that the interaction of Lrrk1-Lrrk2 can form protein dimers and this interaction may influence the age of symptomatic manifestation in Lrrk2-parkinsonism patients.

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