Issue Date: May 14, 2007
Small molecules aid protein degradation
Three newly identified small molecules that help degrade proteins associated with Huntington's and Parkinson's diseases show potential as treatments for these neurodegenerative disorders (Nat. Chem. Biol., DOI: 10.1038/nchembio883). The diseases are identified by the accumulation of mutant huntingtin protein and the aggregation of α-synuclein protein, respectively. In cell cultures, the three compounds (one shown) increased autophagy, a natural cellular mechanism for breaking down and removing unwanted proteins. And in fruit flies developed as a model for Huntington's disease, the enhanced autophagy reduced the neurodegeneration caused by mutant huntingtin. Stuart L. Schreiber of the Broad Institute at Harvard University and MIT, David C. Rubinsztein of the University of Cambridge, and colleagues identified the promising autophagy promoters when they screened more than 50,000 small molecules. The researchers are studying analogs of the compounds that could serve as additional candidates for therapeutic development.
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