title: Autosomal dominant Parkinson's disease and the route to new therapies.
abstract: The pathogenesis of Parkinson's disease (PD) is not understood and there are currently no accepted disease modifying, neuroprotective treatments. There are two autosomal dominant PD genes, leucine-rich repeat kinase (LRRK)2 and alpha-synuclein. LRRK2 mutations are very common in patients with PD, accounting for 40% of patients with sporadic, nonfamilial disease in some ethnic groups. Alpha-synuclein mutations are much less frequent, but the importance of alpha-synuclein has been confirmed by the demonstration of alpha-synuclein deposition as Lewy bodies in patients with PD and Lewy body dementia. Pathogenic mutations in alpha-synuclein accelerate the formation of oligomers and fibrils. Mutations in LRRK2 lead to an enhancement in LRRK2 kinase activity. The further study and understanding of the route by which alpha-synuclein and LRRK2 lead to PD, and how these processes can be therapeutically manipulated, is likely to lead to new disease-modifying treatments.
authors.affiliation: School of Medicine, Cardiff University, CF14 4XN, Wales. morrishr@cf.ac.uk
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
mesh_terms: D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000639:trends; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000517:prevention & control; D015316:Genetic Therapy / Q000379:methods* / Q000639:trends; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D010300:Parkinson Disease / Q000235:genetics* / Q000628:therapy*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D051844:alpha-Synuclein / Q000235:genetics*
chemical_list: D000978:Antiparkinson Agents; D051844:alpha-Synuclein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases