title: α-synuclein, LRRK2 and their interplay in Parkinson's disease.
abstract: Of the various genetic factors contributing to the pathogenesis of Parkinson's disease (PD), only mutations in α-synuclein (α-syn) and LRRK2 genes cause clinical and neuropathological phenotypes closely resembling the sporadic cases. Therefore, studying the pathophysiological functions of these two PD-related genes is particularly informative in understanding the underlying molecular pathogenic mechanism of the disease. PD-related missense and multiplication mutations in α-syn may cause both early- and late-onset PD, whereas various PD-related LRRK2 missense mutations may contribute to the more common late-onset PD. While intensive studies have been carried out to elucidate the pathogenic properties of PD-related mutant α-syn and LRRK2, our knowledge of their normal functions and their potential genetic interplay remains rudimental. In this review, we summarize the progress made regarding the pathophysiological functions of α-syn, LRRK2 and their interaction in PD, based on the available literature and our unpublished observations.
authors.affiliation: Transgenics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Liu
authors.forename: Leonardo
authors.initials: L
authors.lastname: Aliaga
authors.forename: Huaibin
authors.initials: H
authors.lastname: Cai