Overexpression of Rab1 prevents Parkinson-like cell death

{alpha}-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson’s Models — Cooper et al., Science

Fascinating evidence pointing toward a treatment for parkinson’s. Basically, Lindquist’s group finds that overexpression of a trafficking protein Rab1 that moves folded proteins from the ER to the Golgi can prevent alpha-synuclein accumulation-triggered death of rat neurons.

Of course, in vitro is not in vivo. And, for all we know, Parkinson’s could be a complex, multi-mechanism disease. But this looks promising!

Abstract:

Alpha-synuclein misfolding is associated with several devastating neurodegenerative disorders including Parkinson’s Disease (PD). In yeast cells and in neurons {alpha}Syn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following {alpha}Syn expression in yeast was a block in endoplasmic reticulum (ER) to Golgi vesicular trafficking. In a genome-wide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab GTPase Ypt1p, which associated with cytoplasmic {alpha}Syn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD. Thus synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

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4 thoughts on “Overexpression of Rab1 prevents Parkinson-like cell death

  1. How was “Elevated expression of Rab1” accomplished “in animal models of PD.”

    Elevated expression of Rab1, the mammalian YPT1 homolog, protected against {alpha}Syn-induced dopaminergic neuron loss in animal models of PD.

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  2. many agree that alphasynuclein seems to aggregate in PD but what Parkinson’s is comcplex and it seems there are multiple genes responsible. The Penn Genomics institute is doing a whole genomic screen of the multiple genes underlying PD–can these two research projects be brought together

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