Modeling the Critical Activation of Chaperone Machinery in Protein Folding

Abstract

Protein homeostasis is a dynamic network that plays a pivotal role in systems’ maintenance within a cell. This quality control system involves a number of mechanisms regarding the process of protein folding. Chaperones play a critical role in the folding, refolding, and unfolding of proteins. Aggregation of misfolded proteins is a common characteristic of neurodegenerative diseases. Chaperones act in a variety of pathways in this critical interplay between protein homeostasis network and misfolded protein’s load. Moreover, ER stress-induced cell death mechanisms (such as the unfolded protein response) are activated as a response. Therefore, there is a critical balance in the accumulation of misfolded proteins and ER stress response mechanisms which can lead to cell death. Our focus is in understanding the different mechanisms that govern ER stress signaling in health and disease in order to represent the regulation of protein homeostasis and balance of protein synthesis and degradation in the ER. Our proposed model describes, using hybrid modeling, the function of chaperones’ machinery for protein folding.