Sreeganga Chandra
a-Synuclein readily oligomerizes and subsequently aggregates. A large body of work suggests that certain oligomers in the aggregation profile of a-synuclein are the toxic species in Parkinson’s disease. Yet, these oligomers remain to be characterized molecularly.
My project involves identifying these toxic a-synuclein oligomers. I am taking advantage of Thy-1 human A30P a-synuclein transgenic mice, a mouse model for Parkinson’s disease. These mice develop motor phenotypes, a-synuclein pathology and age-dependent neurodegeneration. Due a quirk of genetics, the a-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 a-synuclein oligomers. I am using healthy and phenotypic transgenic pairs to identify a-synuclein oligomers that are only present in phenotypic animals.