NeuroTalk Support Groups - Small molecules found to protect cells in multiple models of Parkinson's disease

http://www.eurekalert.org/pub_releas...-smf122409.php

Small molecules found to protect cells in multiple models of Parkinson's disease
FINDINGS: Several structurally similar small molecules appear capable of protecting cells from alpha-synuclein toxicity, a hallmark of Parkinson's disease...
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Small molecules found to protect cells in multiple models of Parkinson's disease

CAMBRIDGE, Mass. (December 28, 2009) – Several structurally similar small molecules appear capable of protecting cells from alpha-synuclein toxicity in multiple models of Parkinson's disease... Misfolded copies of the alpha-synuclein protein in brain cells are a hallmark of Parkinson's disease.

In their article in Disease Models and Mechanisms (DMM), Lindquist scientists report that four related small molecules prevented the development of several cellular traits associated with Parkinson's disease, including the accumulation of alpha-synuclein deposits in the cell, improper protein trafficking from one organelle to another, and damage inflicted on the cells' engines, the mitochondria.

The research is based on a type of brewer's yeast modified to produce too much of the alpha-synuclein protein in its cells. The resulting cells manifest adverse effects similar to those experienced in brain cells from Parkinson's patients...

In all of the models, the compounds improved protein trafficking and decreased mitochondrial damage...

... "There are very deeply rooted processes that connect protein trafficking and mitochondrial viability," says Lindquist... "That emphasizes that the underlying problem caused by alpha-synuclein is a general cellular defect that is part of the machinery of all eukaryotic cells. The specific problems in Parkinson's are due to the neurons being particularly sensitive to that process going awry."...

"Theoretically if a compound is having a beneficial effect on yeast cells, and in a worm, and in primary neurons, then possibly through years and years of work, it might actually be a potential therapeutic avenue or drug," says Tardiff. "Though we started in yeast, one of those compounds could actually have some potential for human health in Parkinson's disease. That's always a lofty goal."

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The MGH/MIT Morris Udall Center of Excellence in Parkinson Disease Research, the Michael J. Fox Foundation, and the Howard Hughes Medical Institute (HHMI) provided funding for this research.

Full Citation: "Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson disease models"

Disease Models and Mechanisms, published online December 28, 2009

Linhui Julie Su (1,9,*), Pavan K. Auluck (1,3,*), Tiago Fleming Outeiro (1,10 and Susan Lindquist (1,2), et al