%0 Journal Article
%T ¦Á-Synuclein Transgenic Drosophila As a Model of Parkinson's Disease and Related Synucleinopathies
%A Hideya Mizuno
%A Nobuhiro Fujikake
%A Keiji Wada
%A Yoshitaka Nagai
%J Parkinson's Disease
%D 2011
%I Hindawi Publishing Corporation
%R 10.4061/2011/212706
%X ¦Á-Synuclein (¦Á-Syn) is a major component of protein inclusions known as Lewy bodies, which are hallmarks of synucleinopathies such as Parkinson's disease (PD). The ¦Á-Syn gene is one of the familial PD-causing genes and is also associated with an increased risk of sporadic PD. Numerous studies using ¦Á-Syn expressing transgenic animals have indicated that ¦Á-Syn plays a critical role in the common pathogenesis of synucleinopathies. Drosophila melanogaster has several advantages for modeling human neurodegenerative diseases and is widely used for studying their pathomechanisms and therapies. In fact, Drosophila models expressing ¦Á-Syn have already been established and proven to replicate several features of human PD. In this paper, we review the current research on synucleinopathies using ¦Á-Syn Drosophila models and, moreover, explore the possibilities of these models for comprehensive genetic analyses and large-scale drug screening towards elucidating the molecular pathogenesis and developing therapies for synucleinopathies. 1. Introduction Protein inclusions known as Lewy Bodies (LBs) are one of the hallmarks of Parkinson¡¯s disease (PD), in which the major component is now known to be ¦Á-synuclein (¦Á-Syn) [1, 2]. LBs are found in the substantia nigra in PD and also more extensively in other brain regions in other synucleinopathies including multiple system atrophy and dementia with Lewy bodies (DLB) [3, 4]. The ¦Á-Syn encoding gene, SNCA, is the first gene in which missense mutations such as A30P and A53T were found to cause familial PD [5, 6]. Furthermore, the multiplication mutations of ¦Á-Syn gene were also found to cause familial PD [7]. Most importantly, single nucleotide polymorphisms (SNPs) of ¦Á-Syn have been reported to associate with an increased risk of sporadic PD, which comprises the majority of PD patients [8¨C11]. ¦Á-Syn expression has been experimentally shown to mimic several aspects of PD in transgenic animals, such as motor dysfunction, ¦Á-Syn aggregation/accumulation, and neurodegeneration [12¨C14]. These phenotypes are manifested not only by mutations in the ¦Á-Syn gene but also by overexpression of wild-type ¦Á-Syn [15], indicating that ¦Á-Syn plays a critical role in the common pathogenesis of synucleinopathies. Drosophila melanogaster, commonly known as the fruit fly, has been recognized as a powerful organism for modeling human neurodegenerative diseases [16]. At least ~75% of human disease genes have Drosophila homologues [17]. Using Drosophila for modeling human neurodegenerative diseases has various advantages as follows: (1) analysis of
%U http://www.hindawi.com/journals/pd/2011/212706/