Roles of α-Synuclein and Disease-Associated Factors in Drosophila Models of Parkinson's Disease

alpha-Synuclein (alpha Syn) plays a major role in the pathogenesis of Parkinson's disease (PD), which is the second most common neurodegenerative disease after Alzheimer's disease. The accumulation of alpha Syn is a pathological hallmark of PD, and mutations in the SNCA gene encoding alpha Syn cause familial forms of PD. Moreover, the ectopic expression of alpha Syn has been demonstrated to mimic several key aspects of PD in experimental model systems. Among the various model systems, Drosophila melanogaster has several advantages for modeling human neurodegenerative diseases. Drosophila has a well-defined nervous system, and numerous tools have been established for its genetic analyses. The rapid generation cycle and short lifespan of Drosophila renders them suitable for high-throughput analyses. PD model flies expressing alpha Syn have contributed to our understanding of the roles of various disease-associated factors, including genetic and nongenetic factors, in the pathogenesis of PD. In this review, we summarize the molecular pathomechanisms revealed to date using alpha Syn-expressing Drosophila models of PD, and discuss the possibilities of using these models to demonstrate the biological significance of disease-associated factors.

Automated summary

Alpha-synuclein plays a major role in the pathogenesis of Parkinson's disease, and fruit fly models expressing alpha-synuclein contribute to the understanding of disease-associated factors.