title: Genetic LRRK2 models of Parkinson's disease: Dissecting the pathogenic pathway and exploring clinical applications.
abstract: Dominantly inherited mutations in leucine-rich repeat kinase 2 are the most common cause of familial Parkinson's disease. Understanding leucine-rich repeat kinase 2 biology and pathophysiology is central to the elucidation of Parkinson's disease etiology and development of disease intervention. Recently, a number of genetic mouse models of leucine-rich repeat kinase 2 have been reported utilizing different genetic approaches. Some similarities in Parkinson's disease-related pathology emerge in these genetic models despite lack of substantial neuropathology and clinical syndromes of Parkinson's disease. The systematic characterization of these models has begun to shed light on leucine-rich repeat kinase 2 biology and pathophysiology and is expected to offer the identification and validation of drug targets. In this review, we summarize the progress of genetic leucine-rich repeat kinase 2 mouse models and discuss their utility in understanding much needed knowledge regarding early-stage (presymptomatic) disease progression, identifying drug targets, and exploring the potential to aid compound screening focused on inhibitors of kinase activity of leucine-rich repeat kinase 2.
authors.affiliation: Department of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. zhenyu.yue@mssm.edu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yue
authors.forename: M Lenard
authors.initials: ML
authors.lastname: Lachenmayer
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000627:therapeutic use; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology; D009457:Neuroglia / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000977:Antiparasitic Agents; D051844:alpha-Synuclein; D016875:tau Proteins; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases