Issue Date: November 3, 2014
Misfolding Proteins Cut Off At The Pass
Two studies have confirmed that activation of a transcription factor called ATF6 is a valid therapeutic strategy for reducing the secretion and extracellular aggregation of unstable proteins that misfold in human systemic amyloid diseases. Rare systemic amyloid diseases such as light-chain amyloidosis and transthyretin amyloidoses, if left untreated, are lethal conditions caused by the cellular export of mutated proteins that misfold and form aggregates. Current treatments are limited, and more effective ones are needed. R. Luke Wiseman, Jeffery W. Kelly, and coworkers at Scripps Research Institute California report that using a chemical biology method to activate ATF6, a transcription factor in a pathway called the unfolded protein response, promotes proper protein folding and reduces the release of disease-associated misfolding-prone proteins. The treatments substantially reduced the cellular export and extracellular aggregation of mutated immunoglobulin light chains, which cause light-chain amyloidosis (Proc. Natl. Acad. Sci. USA 2014, DOI: 10.1073/pnas.1406050111), and unstable transthyretin, the bad actor in transthyretin amyloidoses (Chem. Biol. 2014, DOI: 10.1016/j.chembiol.2014.09.009). The researchers now hope to identify ATF6-targeted drug candidates as possible amyloidosis treatments.
- Chemical & Engineering News
- ISSN 0009-2347
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