Published in
Springer, Advances in Experimental Medicine and Biology, p. 138-159, 2010
DOI: 10.1007/978-1-4419-7002-2_11
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Protein homeostasis in models of aging and age-related conformational disease
,
Tali Gidalevitz,
Richard I. Morimoto
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Abstract
The stability of the proteome is crucial to the health of the cell, and contributes significantly to the lifespan of the organism. Aging and many age-related diseases have in common the expression of misfolded and damaged proteins. The chronic expression of damaged proteins during disease can have devastating consequences on protein homeostasis (proteostasis), resulting in disruption ofnumerous biological processes. This chapter discusses our current understanding of the various contributors to protein misfolding, and the mechanisms by which misfolding, and accompanied aggregation/toxicity, is accelerated by stress and aging. Invertebrate models have been instrumental in studying the processes related to aggregation and toxicity of disease-associated proteins and how dysregulation ofproteostasis leads to neurodegenerative diseases of aging.