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Sreeganga Chandra

α-Synuclein readily oligomerizes and subsequently aggregates. A large body of work suggests that certain oligomers in the aggregation profile of α-synuclein are the toxic species in Parkinson’s disease. Yet, these oligomers remain to be characterized molecularly.

My project involves identifying these toxic α-synuclein oligomers. I am taking advantage of Thy-1 human A30P α-synuclein transgenic mice, a mouse model for Parkinson’s disease. These mice develop motor phenotypes, α-synuclein pathology and age-dependent neurodegeneration. Due a quirk of genetics, the α-synuclein transgenic phenotypes are not fully penetrant, allowing me to obtain litters of transgenic mice that are healthy, as well as phenotypic. Using the brains of these mice, I have developed a gel chromatography protocol to separate and purify α-synuclein oligomers. I am using healthy and phenotypic transgenic pairs to identify α-synuclein oligomers that are only present in phenotypic animals.