title: Small molecule kinase inhibitors for LRRK2 and their application to Parkinson's disease models.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Several single gene mutations have been linked to this disease. Mutations in the gene encoding leucine-rich repeat kinase 2 (LRRK2) indicate LRRK2 as promising therapeutic target for the treatment of PD. LRRK2 mutations were observed in sporadic as well as familial PD patients and have been investigated intensively. LRRK2 is a large and complex protein, with multiple enzymatic and protein-interaction domains, each of which is effected by mutations. The most common mutation in PD patients is G2019S. Several LRRK2 inhibitors have been reported already, although the crystal structure of LRRK2 has not yet been determined. This review provides a summary of known LRRK2 inhibitors and will discuss recent in vitro and in vivo results of these inhibitors.
authors.affiliation: Clemens Schöpf - Institute of Organic Chemistry and Biochemistry, Technische Universität Darmstadt , 64287 Darmstadt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kramer
authors.forename: Fabio
authors.initials: F
authors.lastname: Lo Monte
authors.forename: Stefan
authors.initials: S
authors.lastname: Göring
authors.forename: Ghislaine Marlyse
authors.initials: GM
authors.lastname: Okala Amombo
authors.forename: Boris
authors.initials: B
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases