Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 131, Issue 3, Pages 210-214Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2010.01.009
Keywords
LRRK2; PD; Dimerization; Genetics; p.G2019S
Categories
Funding
- GlaxoSmithKline
- Neurogenetic Core of a Morris K. Udall Center, National Institute of Neurological Disorders and Stroke [P50 NS40256]
- NIH [R21 NS64885]
- Eli-Lilly
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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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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