title: LRRK2 at the interface of autophagosomes, endosomes and lysosomes.
abstract: Over the past 20 years, substantial progress has been made in identifying the underlying genetics of Parkinson's disease (PD). Of the known genes, LRRK2 is a major genetic contributor to PD. However, the exact function of LRRK2 remains to be elucidated. In this review, we discuss how familial forms of PD have led us to hypothesize that alterations in endomembrane trafficking play a role in the pathobiology of PD. We will discuss the major observations that have been made to elucidate the role of LRRK2 in particular, including LRRK2 animal models and high-throughput proteomics approaches. Taken together, these studies strongly support a role of LRRK2 in vesicular dynamics. We also propose that targeting these pathways may not only be beneficial for developing therapeutics for LRRK2-driven PD, but also for other familial and sporadic cases.
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bldg. 35, 35 Convent Drive, Bethesda, MD, 20892-3707, USA.|School of Pharmacy, University of Reading, Whiteknights, Reading, RG6 6AP, UK.
authors.forename: Dorien A
authors.initials: DA
authors.lastname: Roosen
authors.affiliation: Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bldg. 35, 35 Convent Drive, Bethesda, MD, 20892-3707, USA. cookson@mail.nih.gov.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
mesh_terms: D000818:Animals; D000071182:Autophagosomes / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics* / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D021381:Protein Transport / Q000235:genetics / Q000502:physiology*
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: GTPases; Membrane proteins; Parkinson’s disease; Protein kinases; Vesicular trafficking