title: Insights into LRRK2 function and dysfunction from transgenic and knockout rodent models.
abstract: Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene on chromosome 12 cause autosomal dominant PD (Parkinson's disease), which is indistinguishable from sporadic forms of the disease. Numerous attempts have therefore been made to model PD in rodents via the transgenic expression of LRRK2 and its mutant variants and to elucidate the function of LRRK2 by knocking out rodent Lrrk2. Although these models often only partially recapitulate PD pathology, they have helped to elucidate both the normal and pathological function of LRRK2. In particular, LRRK2 has been suggested to play roles in cytoskeletal dynamics, synaptic machinery, dopamine homoeostasis and autophagic processes. Our understanding of how these pathways are affected, their contribution towards PD development and their interaction with one another is still incomplete, however. The present review summarizes the findings from LRRK2 rodent models and draws potential connections between the apparently disparate cellular processes altered, in order to better understand the underlying mechanisms of LRRK2 dysfunction and illuminate future therapeutic interventions.
authors.affiliation: Oxford Parkinson's Disease Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, U.K.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Sloan
authors.forename: Javier
authors.initials: J
authors.lastname: Alegre-Abarrategui
authors.forename: Richard
authors.initials: R
authors.lastname: Wade-Martins
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017353:Gene Deletion; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; C495279:Lrrk2 protein, mouse; D017346:Protein Serine-Threonine Kinases