Diacetyl Exacerbates Amyloid Toxicity

Diacetyl, the molecule implicated in the disease known as popcorn lung, has now been implicated in amyloid-β peptide toxicity associated with Alzheimer’s disease (Chem. Res. Toxicol., DOI: 10.1021/tx3001016). Diacetyl, or 2,3-butanedione, is infamous as a butter-flavor compound tied to the rare lung disease responsible for the deaths of some workers at microwave popcorn plants. Microwave popcorn makers stopped using diacetyl flavoring in 2006. Swati S. More, Ashish P. Vartak, and Robert Vince of the University of Minnesota’s Center for Drug Design have now found in cell-culture studies that diacetyl accelerates amyloid-β aggregation—a hallmark of Alzheimer’s disease. Diacetyl was also found to inhibit glyoxalase I, an enzyme that helps detoxify reactive dicarbonyl species similar to diacetyl that are produced in neurons and promote amyloid aggregation. In addition, diacetyl tested positive in an in vitro assay to determine if compounds can cross the blood-brain barrier. In light of the chronic exposure of some food industry workers to diacetyl, these preliminary findings raise the possibility of long-term neurological toxicity, Vince and coworkers state. The findings come on the heels of research on amyloid-β suggesting that it might behave like prion protein associated with mad cow disease and be infectious (C&EN, July 2, page 24).