The role of Rab GTPases in the pathobiology of Parkinson' disease. (August 2019)

• Record Type: Journal Article
• Authors: Bonet-Ponce, Luis; Cookson, Mark R
• Is Part Of: Current opinion in cell biology. Volume 59(2019)
• Page Start: 73
• Page End: 80
• Publication Date: 2019-08
• Subjects: Cells -- Periodicals; Cytology -- Periodicals; Cell Biology -- Periodicals; Biology -- Periodicals; Cells -- Periodicals; Review Literature -- Periodicals; Cell Biology; Biology; Cells; Review Literature; Cellules -- Périodiques; Cytologie -- Périodiques; Electronic journals; 571.6
• DOI: 10.1016/j.ceb.2019.03.009
• Languages: English
• ISSNs: 0955-0674

Abstract

Highlights: Recent advances in human genetics point to membrane trafficking as a key pathway in Parkinson's disease (PD). LRRK2 phosphorylates fourteen different Rab proteins in a conserved residue in the Switch II domain. By phosphorylating its Rab substrates, LRRK2 regulates ciliogenesis, centrosome dynamics and lysosomal exocytosis. Different Rab GTPases act as α-synuclein regulators by controlling its aggregation, clearance and propagation. By phosphorylating Rab35, LRRK2 promotes the propagation of α-synuclein aggregates (a proposed mechanism for PD progression). Abstract : Rab GTPases are key regulators of vesicle-mediated transport and are proposed to play a crucial role in the pathobiology of Parkinson's disease. As membrane trafficking seems to be a relevant pathway altered in Parkinson' disease, understanding the role of Rab GTPases in the disease progression could open a window for therapeutic interventions. In this review, we focus on the recent advances on the role of Rab GTPases in the biology of two main proteins involved in Parkinson's disease: LRRK2 and α-synuclein, given that mutations in their genes ( LRRK2 and SNCA ) cause familial and sporadic Parkinson's disease.