AANS Neurosurgeon | Volume 26, Number 1, 2017

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New Clues on the Base of Parkinson's Disease and Other "Synucleinopathies"

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New techniques map alpha-syuclein toxicity, spatial location and links to Parkinson’s genes

Parkinson’s disease (PD) and other “synucleinopathies” are known to be linked to the misfolding of alpha-synuclein protein in neurons. Less clear is how this misfolding relates to the growing number of genes implicated in PD through analysis of human genetics. In two studies, researchers affiliated with Whitehead Institute and Massachusetts Institute of Technology (MIT) explain how they used a suite of novel biological and computational methods to shed light on the question. To start, they created two ways to systematically map the footprint of alpha-synuclein within living cells. “In the first paper, we used powerful and unbiased genetic tools in the simple Baker’s yeast cell to identify 332 genes that impact the toxicity of alpha-synuclein,” explained Vikram Khurana, first and co-corresponding author on the studies. “Among them were multiple genes known to predispose individuals to Parkinson’s—so we show that various genetic forms of Parkinson’s are directly related to alpha-synuclein. Moreover, the results showed that many effects of alpha-synuclein have been conserved across a billion years of evolution from yeast to human,” said Khurana, former visiting scientist at the Whitehead Institute.

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