An in silico model of the ubiquitin-proteasome system that incorporates normal homeostasis and age-related decline.

ABSTRACT:

Background

The ubiquitin-proteasome system is responsible for homeostatic degradation of intact protein substrates as well as the elimination of damaged or misfolded proteins that might otherwise aggregate. During ageing there is a decline in proteasome activity and an increase in aggregated proteins. Many neurodegenerative diseases are characterised by the presence of distinctive ubiquitin-positive inclusion bodies in affected regions of the brain. These inclusions consist of insoluble, unfolded, ubiquitinated polypeptides that fail to be targeted and degraded by the proteasome. We are using a systems biology approach to try and determine the primary event in the decline in proteolytic capacity with age and whether there is in fact a vicious cycle of inhibition, with accumulating

SUBMITTER: Proctor CJ 

PROVIDER: S-EPMC1847462 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature