New Autophagy-Enhancing Molecules Found

A team of British and U.S. scientists has found small molecules that act by increasing autophagy, becoming potential treatments for Huntington’s disease.

Autophagy — a biological process in which cells eat part of their own cytoplasm — is known to be important for removing aggregation-prone proteins that contribute to causing neurodegenerative disease. Therefore, enhancing autophagy is a potential strategy for treating such diseases.

However, the researchers said rapamycin — the only known small molecule that increases autophagy — regulates a wide range of cellular processes and would have too many side effects to be a useful therapeutic.

David Rubinsztein of the University of Cambridge, Stuart Schreiber of Harvard University’s Broad Institute and the Massachusetts Institute of Technology, and colleagues have used a chemical screen in yeast to identify three new small molecules, called SMERs, that also enhance autophagy.

The researchers have demonstrated the new compounds inhibit disease progression in mammalian cell and Drosophila melanogaster models of Huntington’s disease, thereby providing an important new therapeutic avenue.

Their research is reported in the June issue of the journal Nature Chemical Biology.