Pathogenic LRRK2 variants are gain-of-function mutations that enhance LRRK2-mediated repression of β-catenin signaling

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• 作者：Daniel C. Berwick ; Behzad Javaheri ; Andrea Wetzel…
• 关键词：LRRK2 ; β ; catenin ; Parkinson’s disease ; Wnt signaling ; Osteoporosis
• 刊名：Molecular Neurodegeneration
• 出版年：2017
• 出版时间：December 2017
• 年：2017
• 卷：12
• 期：1
• 全文大小：1522KB
• 刊物主题：Neurosciences; Neurology; Molecular Medicine;
• 出版者：BioMed Central
• ISSN：1750-1326
• 卷排序：12

文摘

BackgroundLRRK2 mutations and risk variants increase susceptibility to inherited and idiopathic Parkinson’s disease, while recent studies have identified potential protective variants. This, and the fact that LRRK2 mutation carriers develop symptoms and brain pathology almost indistinguishable from idiopathic Parkinson’s disease, has led to enormous interest in this protein. LRRK2 has been implicated in a range of cellular events, but key among them is canonical Wnt signalling, which results in increased levels of transcriptionally active β-catenin. This pathway is critical for the development and survival of the midbrain dopaminergic neurones typically lost in Parkinson’s disease.