Tuesday 2 December 2003
Stress to the cell causes protein denaturation: the protein molecule loses its native functional conformation when it unfolds. Chaperones assist the damaged molecule to regain its functional conformation.
If cellular stress proceeds unchecked by such antistress mechanisms as the protein-refolding action of chaperones, intracellular proteins become denatured and insoluble.
These denatured proteins tend to stick to one another, precipitate, and form inclusion bodies. The development of inclusion bodies is a common pathologic process in Parkinson disease, Alzheimer disease, and Huntington disease, even in the absence of cellular stress.
Denatured and aggregated proteins cannot function and must either be rescued or eliminated with the help of chaperone proteins.
- neuronal stress responses
stress-activated protein kinases
Macario AJ, Conway de Macario E. Sick chaperones, cellular stress, and disease. N Engl J Med. 2005 Oct 6;353(14):1489-501. PMID: 16207851
Beere HM, Green DR. Stress management - heat shock protein-70 and the regulation of apoptosis. Trends Cell Biol. 2001 Jan;11(1):6-10. PMID: 11146277