title: Leucine-rich repeat kinase 2 (LRRK2) as a potential therapeutic target in Parkinson's disease.
abstract: Parkinson's disease (PD) is caused by the progressive degeneration of dopaminergic neurons in the substantia nigra. Although the etiology for most PD remains elusive, the identification of specific genetic defects in familial cases of PD and the signaling pathways governed by these genes has provided tremendous insight into PD pathogenesis. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are frequently found in familial and sporadic PD. Although current knowledge regarding the regulatory mechanisms of LRRK2 activation is limited, it is becoming increasingly evident that aberrant kinase activity of the pathologic mutants of LRRK2 is associated with neurodegeneration, suggesting that the kinase activity of LRRK2 is a potential therapeutic target. In addition, LRRK2 inhibitors might provide valuable tools to understand the pathophysiological and physiological roles of LRRK2 as well as the etiology of PD. We discuss here the potential and feasibility of targeting LRRK2 as a therapeutic strategy for PD.
authors.affiliation: Age-Related and Brain Disease Research Center, Kyung Hee University, Seoul, South Korea.
authors.forename: Byoung Dae
authors.initials: BD
authors.lastname: Lee
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000737:chemistry / Q000627:therapeutic use; D017173:Caenorhabditis elegans / Q000235:genetics; D004195:Disease Models, Animal; D004330:Drosophila / Q000235:genetics; D015195:Drug Design; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D009154:Mutation; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases