Parkinson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Parkinson's Disease, including details on symptoms, treatment, genetics, medication.

Hypothesis-based RNAi screening identifies neuroprotective genes in a Parkinson's disease model.

Hamamichi S, Rivas RN, Knight AL, Cao S, Caldwell KA, Caldwell GA

Department of Biological Sciences, University of Alabama, Tuscaloosa, AL 35487, USA.

Genomic multiplication of the locus-encoding human alpha-synuclein (alpha-syn), a polypeptide with a propensity toward intracellular misfolding, results in Parkinson's disease (PD). Here we report the results from systematic screening of nearly 900 candidate genetic targets, prioritized by bioinformatic associations to existing PD genes and pathways, via RNAi knockdown. Depletion of 20 gene products reproducibly enhanced misfolding of alpha-syn over the course of aging in the nematode Caenorhabditis elegans. Subsequent functional analysis of seven positive targets revealed five previously unreported gene products that significantly protect against age- and dose-dependent alpha-syn-induced degeneration in the dopamine neurons of transgenic worms. These include two trafficking proteins, a conserved cellular scaffold-type protein that modulates G protein signaling, a protein of unknown function, and one gene reported to cause neurodegeneration in knockout mice. These data represent putative genetic susceptibility loci and potential therapeutic targets for PD, a movement disorder affecting approximately 2% of the population over 65 years of age.

Published 16 January 2008 in Proc Natl Acad Sci U S A, 105(2): 728-33.
Full-text of this article is available online (may require subscription).

© 2004-2008 Parkinson's Disease Research Today. All Rights Reserved.