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Scientists uncover strong support for once-marginalized theory on Parkinson's disease
Date:4/25/2012

University of California, San Diego scientists have used powerful computational tools and laboratory tests to discover new support for a once-marginalized theory about the underlying cause of Parkinson's disease.

The new results conflict with an older theory that insoluble intracellular fibrils called amyloids cause Parkinson's disease and other neurodegenerative diseases. Instead, the new findings provide a step-by-step explanation of how a "protein-run-amok" aggregates within the membranes of neurons and punctures holes in them to cause the symptoms of Parkinson's disease.

The discovery, published in the March 2012 issue of the FEBS Journal, describes how α-synuclein (a-syn), can turn against us, particularly as we age. Modeling results explain how α-syn monomers penetrate cell membranes, become coiled and aggregate in a matter of nanoseconds into dangerous ring structures that spell trouble for neurons.

"The main point is that we think we can create drugs to give us an anti-Parkinson's effect by slowing the formation and growth of these ring structures," said Igor Tsigelny, lead author of the study and a research scientist at the San Diego Supercomputer Center and Department of Neurosciences, both at UC San Diego.

Familial Parkinson's disease is caused in many cases by a limited number of protein mutations. One of the most toxic is A53T. Tsigelny's team showed that the mutant form of α-syn not only penetrates neuronal membranes faster than normal α-syn, but the mutant protein also accelerates ring formation.

"The most dangerous assault on the neurons of Parkinson's patients appears to be the relatively small α-syn ring structures themselves," said Tsigelny. "It was once heretical to suggest that these ring structures, rather than long fibrils found in neurons of people having Parkinson's disease, were responsible for the symptoms of the disease; however, the ring theory is becoming
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Contact: Rex Graham
ragraham@ucsd.edu
858-232-2706
University of California - San Diego
Source:Eurekalert

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