Modelling the role of UCH-L1 on protein aggregation in age-related neurodegeneration.

ABSTRACT: Overexpression of the de-ubiquitinating enzyme UCH-L1 leads to inclusion formation in response to proteasome impairment. These inclusions contain components of the ubiquitin-proteasome system and α-synuclein confirming that the ubiquitin-proteasome system plays an important role in protein aggregation. The processes involved are very complex and so we have chosen to take a systems biology approach to examine the system whereby we combine mathematical modelling with experiments in an iterative process. The experiments show that cells are very heterogeneous with respect to inclusion formation and so we use stochastic simulation. The model shows that the variability is partly due to stochastic effects but also depends on protein expression levels of UCH-L1 within cells. The model also indicat

SUBMITTER: Proctor CJ 

PROVIDER: S-EPMC2950841 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature