Modeling of human parkinson’s disease in fly

Abstract

Years of in-depth research have contributed substantially to the understanding of the pathophysiology of Parkinson’s diseases (PD). However, many crucial questions related to the etiology of the disease remain unanswered, which compelled the need for developing more realistic and genetically malleable model systems for modeling the precise neuropathology of the disease in vivo. Ever-expanding genetic toolkit and conservation of implicated signaling pathways and neurological properties have prompted the use of Drosophila melanogaster (fly) as an instrumental model. Humanized fly models have aided in gaining insight into different cellular disturbances (protein aggregation and misfolding), mitochondrial deficits, and oxidative stress toward causation of Parkinson’s disease. The transgenic and humanized Drosophila model provides a decisive platform to assess the pathogenic properties of rare variants and open a window to analyze the cellular processes and signaling pathways that have been disrupted, which is ultimately manifested by the death of dopaminergic neurons in the brain of Parkinson-affected subjects. Apart from gaining molecular insight, toxin-induced models of Drosophila recapitulate multiple symptoms of environmental toxin-induced PD. Environmental toxin-induced models of Drosophila have proven to be an efficient means to study gene-environment interactions, which elevate susceptibility for Parkinsonism. Employment of Drosophila to scrutinize gene-environment interactions has led to the screening of many genetic risk factors. Additionally, the rapid development of genome manipulation technologies have paced up the development of more realistic models, which can precisely replicate all pathological features of the disease. This should be worthwhile to elucidate uncharted genetic and environmental risk factors, which are responsible for the complex pathogenesis associated with Parkinson’s disease. The ease of genetic manipulations that mimic symptoms of PD in Drosophila makes it one of the most favorite model organisms for analyzing the underlying cause of PD, the second most prevalent neurological disorder after Alzheimer’s disease. © Springer Nature Singapore Pte Ltd. 2019.