TAILIEUCHUNG - Báo cáo khoa học: LRRK2 in Parkinson’s disease: in vivo models and approaches for understanding pathogenic roles

The recent discovery of the genetic causes for Parkinson’s disease (PD) is fruitful; however, the continuing revelation of PD-related genes is rapidly outpacing the functional characterization of the gene products. Although the discovery of multiple PD-related genes places PD as one of the most complex multigenetic diseases of the brain, it will undoubtedly facilitate the unfolding of a central pathogenic pathway and an understanding of the eti-ology of PD. | ỊFEBS Journal MINIREVIEW LRRK2 in Parkinson s disease in vivo models and approaches for understanding pathogenic roles Zhenyu Yue Department of Neurology and Neuroscience Mount Sinai Schoolof Medicine New York NY USA Keywords animal models BAC transgenics dopamine GTPase kinase leucine-rich repeat kinase 2 LRRK2 Parkinson s disease pathogenesis ROCO Correspondence Z. Yue Department of Neurology and Neuroscience Mount Sinai School of Medicine New York NY 10029 USA Fax 1 212 241 3869 Tel 1 212 241 3155 E-mail Received 30 May 2009 revised 30 July 2009 accepted 18 August 2009 doi The recent discovery of the genetic causes for Parkinson s disease PD is fruitful however the continuing revelation of PD-related genes is rapidly outpacing the functional characterization of the gene products. Although the discovery of multiple PD-related genes places PD as one of the most complex multigenetic diseases of the brain it will undoubtedly facilitate the unfolding of a central pathogenic pathway and an understanding of the etiology of PD. Recent findings of pathogenic mutations in leucine-rich repeat kinase 2 LRRK2 PARK8 that are linked to the most common familial forms and some sporadic forms of PD provide a unique opportunity to gain insight into the pathogenesis of PD. Despite rapid growth in biochemical structural and in vitro cell culture studies of LRRK2 the in vivo characterizations of LRRK2 function generally fall short and are largely limited to invertebrates. The investigation of LRRK2 or homologs of LRRK2 in nonmammalian models provides important clues with respect to the cellular functions of LRRK2 but an elucidation of the physiology and pathophysiology of LRRK2 relevant to PD would still depend on mammalian models established by multiple genetic approaches followed by rigorous examination of the models for pathological process. This minireview summarizes previous studies of genes for ROCO and LRRK2 homologs in .

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