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Modelling the actions of chaperones and their role in ageing

Lookup NU author(s): Dr Carole Proctor, Professor Richard Boys, Dr Colin Gillespie, Dr Daryl Shanley, Professor Darren Wilkinson, Emeritus Professor Thomas Kirkwood

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Abstract

Many molecular chaperones are also known as heat shock proteins because they are synthesised in increased amounts after brief exposure of cells to elevated temperatures. They have many cellular functions and are involved in the folding of nascent proteins, the re-folding of denatured proteins, the prevention of protein aggregation, and assisting the targeting of proteins for degradation by the proteasome and lysosomes. They also have a role in apoptosis and are involved in modulating signals for immune and inflammatory responses. Stress-induced transcription of heat shock proteins requires the activation of heat shock factor (HSF). Under normal conditions. HSF is bound to heat shock proteins resulting in feedback repression. During stress, cellular proteins undergo denaturation and sequester heat shock proteins bound to HSF, which is then able to become transcriptionally active. The induction of heat shock proteins is impaired with age and there is also a decline in chaperone function. Aberrant/damaged proteins accumulate with age and are implicated in several important age-related conditions (e.g. Alzheimer's disease. Parkinson's disease. and cataract). Therefore, the balance between damaged proteins and available free chaperones may be greatly disturbed during ageing. We have developed a mathematical model to describe the heat shock system. The aim of the model is two-fold: to explore the beat shock system and its implications in ageing; and to demonstrate how to build a model of a biological system using our simulation system (biology of ageing e-science integration and simulation (BASIS)). (C) 2004 Elsevier Ireland Ltd. All rights reserved.


Publication metadata

Author(s): Proctor CJ, Soti C, Boys RJ, Gillespie CS, Shanley DP, Wilkinson DJ, Kirkwood TBL

Publication type: Article

Publication status: Published

Journal: Mechanisms of Ageing and Development

Year: 2005

Volume: 126

Issue: 1

Pages: 119-131

ISSN (print): 0047-6374

ISSN (electronic): 1872-6216

Publisher: Elsevier Ireland Ltd

URL: http://dx.doi.org/10.1016/j.mad.2004.09.031

DOI: 10.1016/j.mad.2004.09.031


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