Genetics of Parkinson's Disease—An Overview

3 Citations (Scopus)


This chapter provides an overview of the genetics of Parkinson's disease (PD). Studying the effect of mutations in PD genes has provided unique opportunities to pursue the mechanisms of neuronal degeneration in parkinsonism, highlighting the significance of oxidative stress, mitochondrial dysfunction, and impaired protein turnover. A model of common pathways underlying genetic parkinsonism and idiopathic PD is presented with impaired protein degradation, mitochondrial dysfunction, and oxidative damage as key elements. In the chapter, the monogenic forms of parkinsonism with a PARK acronym are grouped according to their mode of inheritance. The α-synuclein (SNCA) gene is discussed as it was the first one to be unequivocally associated with familial parkinsonism. The mechanism underlying SNCA overexpression, which is represented by different, ethnically dependent patterns of association to various SNCA polymorphisms, is elucidated. Ubiquitin carboxyterminal hydrolase 1 (UCHL1), as one of the key players in protein degradation, is a plausible candidate to be involved in the pathogenesis of parkinsonism. The leucine-rich repeat kinase 2 (LRRK2) () is the only gene that plays a considerable, albeit mostly small, role in late-onset sporadic parkinsonism, with mutation frequencies ranging from 2% to 40%. The chapter discusses the mutation leucine-rich repeat kinase 2 (LRRK2), Omi/HtrA2, parkin, PTEN-induced kinase 1 (PINK1), DJ-1, and ATP13A2. The chapter also discusses digenic parkinsonism, monogenic parkinsonism without a park acronym, parkinsonism associated with mutations in non-park genes, genetic susceptibility factors for Parkinson's disease, genetic testing for parkinsonism, and novel therapeutic strategies for parkinsonism.

Original languageEnglish
Title of host publicationBlue Books of Neurology
Number of pages25
Publication date01.01.2010
Publication statusPublished - 01.01.2010


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