Title
Parkinson’s disease associated α-synuclein familial mutants promote dopaminergic neuronal death in Drosophila melanogaster
Author
Ganesh M Mohite, Saumya Dwivedi, Subhadeep Das, Rakesh Kumar, sravya paluri, Surabhi Mehra, Neha Ruhela, Arunima S, Narendra Nath Jha, Samir K. Maji
Year
2018
Journal
ACS Chemical Neuroscience
Abstract
α-Synuclein (α-Syn) aggregation and amyloid formation are associated with loss of dopaminergic neurons in Parkinson’s disease (PD). In addition, familial mutations in α-Syn are shown to be one of the definite causes of PD. Here we have extensively studied familial PD associated α-Syn G51D, H50Q and E46K mutations using Drosophila model system. Our data showed that flies expressing α-Syn familial mutants have a shorter lifespan and exhibit more climbing defects compared to wild-type (WT) flies in an age-dependent manner. The immuno-fluorescence studies of the brain from the old flies showed more dopaminergic neuronal cell death in all mutants compared to WT. This adverse effect of α-Syn familial mutations highly correlated with the sustained population of oligomer production/ retention in mutant flies. Furthermore, this was supported by our in vitro studies, where significantly higher amount of oligomer was observed in mutants compared to WT. The data suggest that the sustained population of oligomer formation/ retention could be a major cause of cell death by α-Syn familial mutants.
Instrument
J-1500
Keywords
Circular dichroism, Secondary structure, Aggregation, Biochemistry