کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1919468 1535647 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Heterodimerization of Lrrk1–Lrrk2: Implications for LRRK2-associated Parkinson disease
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Heterodimerization of Lrrk1–Lrrk2: Implications for LRRK2-associated Parkinson disease
چکیده انگلیسی

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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mechanisms of Ageing and Development - Volume 131, Issue 3, March 2010, Pages 210–214
نویسندگان
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