Justus C Dächsel1, Matthew J Farrer. 1. Laboratories of Neurogenetics, Department of Neuroscience, Morris K. Udall Parkinson's Disease Research Center of Excellence, Mayo Clinic, Jacksonville, Florida 32224, USA.
Abstract
OBJECTIVES: To review the molecular genetics and functional biology of leucine-rich repeat kinase 2 (LRRK2) in parkinsonism and to summarize the opportunities and challenges to develop interventions for Parkinson disease (PD) based on this genetic insight. DATA SOURCES: Publications cited are focused on LRRK2 biology between 2004 and March 2009. STUDY SELECTION: Literature selected was based on original contributions, seminal observations, and thoughtful reviews. DATA EXTRACTION: Unless stated otherwise, data was primarily abstracted from peer-reviewed literature appearing on PubMed. DATA SYNTHESIS: Genetic mutations that predispose PD are diagnostically useful in early or atypical presentations. The molecular pathways identified suggest therapeutic interventions for Lrrk2 and idiopathic PD and the rationale and opportunity to develop physiologically relevant biomarkers and experimental models with which to test them. CONCLUSIONS: Both affected and asymptomatic LRRK2 carriers now provide the opportunity to define the natural history of PD. This includes the frequency, penetrance, and rate of motor symptoms, nonmotor comorbidities, and their associated biomarkers.
OBJECTIVES: To review the molecular genetics and functional biology of leucine-rich repeat kinase 2 (LRRK2) in parkinsonism and to summarize the opportunities and challenges to develop interventions for Parkinson disease (PD) based on this genetic insight. DATA SOURCES: Publications cited are focused on LRRK2 biology between 2004 and March 2009. STUDY SELECTION: Literature selected was based on original contributions, seminal observations, and thoughtful reviews. DATA EXTRACTION: Unless stated otherwise, data was primarily abstracted from peer-reviewed literature appearing on PubMed. DATA SYNTHESIS: Genetic mutations that predispose PD are diagnostically useful in early or atypical presentations. The molecular pathways identified suggest therapeutic interventions for Lrrk2 and idiopathic PD and the rationale and opportunity to develop physiologically relevant biomarkers and experimental models with which to test them. CONCLUSIONS: Both affected and asymptomatic LRRK2 carriers now provide the opportunity to define the natural history of PD. This includes the frequency, penetrance, and rate of motor symptoms, nonmotor comorbidities, and their associated biomarkers.
Authors: Owen A Ross; Alexandra I Soto-Ortolaza; Michael G Heckman; Jan O Aasly; Nadine Abahuni; Grazia Annesi; Justin A Bacon; Soraya Bardien; Maria Bozi; Alexis Brice; Laura Brighina; Christine Van Broeckhoven; Jonathan Carr; Marie-Christine Chartier-Harlin; Efthimios Dardiotis; Dennis W Dickson; Nancy N Diehl; Alexis Elbaz; Carlo Ferrarese; Alessandro Ferraris; Brian Fiske; J Mark Gibson; Rachel Gibson; Georgios M Hadjigeorgiou; Nobutaka Hattori; John P A Ioannidis; Barbara Jasinska-Myga; Beom S Jeon; Yun Joong Kim; Christine Klein; Rejko Kruger; Elli Kyratzi; Suzanne Lesage; Chin-Hsien Lin; Timothy Lynch; Demetrius M Maraganore; George D Mellick; Eugénie Mutez; Christer Nilsson; Grzegorz Opala; Sung Sup Park; Andreas Puschmann; Aldo Quattrone; Manu Sharma; Peter A Silburn; Young Ho Sohn; Leonidas Stefanis; Vera Tadic; Jessie Theuns; Hiroyuki Tomiyama; Ryan J Uitti; Enza Maria Valente; Simone van de Loo; Demetrios K Vassilatis; Carles Vilariño-Güell; Linda R White; Karin Wirdefeldt; Zbigniew K Wszolek; Ruey-Meei Wu; Matthew J Farrer Journal: Lancet Neurol Date: 2011-08-30 Impact factor: 44.182