Abstract
Parkinson’s disease (PD) is recognized as the second most common neurodegenerative disorder after Alzheimer’s disease. Unfortunately, there is no cure or proven disease modifying therapy for PD. The recent discovery of a number of genes involved in both sporadic and familial forms of PD has enabled disease modeling in easily manipulable model systems. Various model systems have been developed to study the pathobiology of PD and provided tremendous insights into the molecular mechanisms underlying dopaminergic neurodegeneration. Among all the model systems, the power of Drosophila has revealed many genetic factors involved in the various pathways, and provided potential therapeutic targets. This review focuses on Drosophila models of PD, with emphasis on how Drosophila models have provided new insights into the mutations of dominant genes causing PD and what are the convergent mechanisms.
Highlights
Parkinson’s disease (PD) is recognized as the most common movement disorder and the second most common neurodegenerative disorder after Alzheimer’s disease [1]
Genes encoding α-synuclein (α-Syn), leucine-rich repeat kinase 2 (LRRK2), Parkin, phosphatase and tensin homolog deleted on chromosome 10-induced putative kinase 1 (PINK1), DJ-1, vacuolar protein sorting 35 (VPS35), and glucocerebrosidase (GBA), among others are associated with genetic forms of PD that closely resemble idiopathic PD [3,4,5,6,7,8]
Drosophila have no homolog of SNCA, pathogenic mutations and multiplication of SNCA causing PD with dominant inheritance pattern implicates a toxic gain-of-function mechanism, which led to suitable transgenic modeling in fly by overexpressing wild-type or mutant α-Syn [69] (Table 2)
Summary
Parkinson’s disease (PD) is recognized as the most common movement disorder and the second most common neurodegenerative disorder after Alzheimer’s disease [1]. In contrast to dLRRK loss-of-function mutant, overexpression of either human LRRK2 (hLRRK2) or dLRRK pathogenic mutations in flies leads to an age-dependent DA neuronal loss and DA-responsive locomotor deficits [28, 30,31,32,33, 36, 37]. Drosophila have no homolog of SNCA, pathogenic mutations and multiplication of SNCA causing PD with dominant inheritance pattern implicates a toxic gain-of-function mechanism, which led to suitable transgenic modeling in fly by overexpressing wild-type or mutant α-Syn [69] (Table 2).
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