Chaperone overload is a possible contributor to 'civilization diseases'.
Molecular chaperones dampen the effect of damaging mutations that would otherwise be removed from the population by natural selection. Here, I propose that the development of modern medical practice depressed this process, leading to a rise of phenotypically silent mutations in the genome. The background of misfolded proteins increases during ageing and, by competition, prevents the chaperone-mediated buffering of silent mutations. Phenotypically exposed mutations contribute to a more-abundant manifestation of multigene-diseases. This 'chaperone overload' hypothesis emphasizes the need for efficient ways to enhance chaperone capacity in ageing subjects, and will hopefully lead to the identification and 'repair' of silent mutations.
Csermely
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Dept of Medical Chemistry, Semmelweis University, PO Box 260, H-1444 Budapest, Hungary. csermely@puskin.sote.hu
D000375:Aging / Q000235:genetics; D002962:Civilization; D004252:DNA Mutational Analysis; D004194:Disease; D014644:Genetic Variation; D015894:Genome, Human; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D008957:Models, Genetic; D018832:Molecular Chaperones / Q000502:physiology*; D009154:Mutation; D017510:Protein Folding
D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones