Activation of the ubiquitin-proteasome system: implications for neurodegeneration, aging, and tumorigenesis

Abstract

Since the discovery of the proteasome (1986), many years passed before researchers explored the benefits of its activation. However, its inhibition, which was first observed in the beginning of the 1990s, gained wide acceptance because of its anti-tumor effect, as proteasome inhibition induces apoptosis. Currently, a proteasome inhibitor is utilized as a clinical tool. However, proteasome activation has been shown to either extend the life span of many cellular and animal models or prevent the accumulation of protein aggregates. Later effect might have an important contribution to neurodegenerative diseases with the hallmark of protein aggregation and the impairment of the proteasome. This short review presents prominent data on proteasome activation, focusing on the 20S catalytic proteasome particle. In addition, the benefits and consequences of proteasome activation in tumor development and progression are discussed.

Brain ageing and neurodegenerative disease: The role of cellular waste management

“…The proteasome comprises a central catalytic core named 20S that comprises 28 subunits present in four heptamers in a cylinder shape. It has been demonstrated that the proteasome functionality declines during the ageing process and triggers the onset of age-related diseases and neurodegeneration [11]. The UPS activation is able to extend the life span in several species and cellular models [11].…”

“…It has been demonstrated that the proteasome functionality declines during the ageing process and triggers the onset of age-related diseases and neurodegeneration [11]. The UPS activation is able to extend the life span in several species and cellular models [11].…”