The proteasome is a construct in cells that shreds damaged, misfolded, or unwanted proteins, reducing them to component parts that can be reused. It is a part of the ubuiquitin-proteasome system: molecules to be destroyed are tagged with ubiquitin, and drawn into a proteasome for recycling. Greater proteasome activity is thought to be a good thing, improving cell function. This is of particular relevance to aging, as proteasomal function declines with age, contributing to faltering cell and tissue function, particularly in the long-lived cells of the nervous system.

While established drugs exist to inhibit activity of the proteasome, useful in cancer therapies in which cell death is a goal, improving proteasomal activity is less well explored. The one approach shown to work well to date is to increase expression of some of the individual rate-limiting proteins that make up proteasomal structure. This has been shown to extend life in short-lived laboratory species, an enhancement therapy that partially compensates for the progressive loss of proteasomal function with age. Researchers here outline their discovery of a different methodology, one that may be more amenable to the production of a drug capable of upregulating proteasome function.

New Peptide-Based Pharmacophore Activates 20S Proteasome