title: Mechanisms of protein homeostasis in health, aging and disease.
abstract: When emerging from the ribosomes, new polypeptides need to fold properly, eventually translocate, and then assemble into stable, yet functionally flexible complexes. During their lifetime, native proteins are often exposed to stresses that can partially unfold and convert them into stably misfolded and aggregated species, which can in turn cause cellular damage and propagate to other cells. In animal cells, especially in aged neurons, toxic aggregates may accumulate, induce cell death and lead to tissue degeneration via different mechanisms, such as apoptosis as in Parkinson's and Alzheimer's diseases and aging in general. The main cellular mechanisms effectively controlling protein homeostasis in youth and healthy adulthood are: (1) the molecular chaperones, acting as aggregate unfolding and refolding enzymes, (2) the chaperone-gated proteases, acting as aggregate unfolding and degrading enzymes, (3) the aggresomes, acting as aggregate compacting machineries, and (4) the autophagosomes, acting as aggregate degrading organelles. For unclear reasons, these cellular defences become gradually incapacitated with age, leading to the onset of degenerative diseases. Understanding these mechanisms and the reasons for their incapacitation in late adulthood is key to the design of new therapies against the progression of aging, degenerative diseases and cancers.
authors.affiliation: Department of Plant Molecular Biology, Faculty of Biology and Medicine, Lausanne University, Lausanne,Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Goloubinoff
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000378:metabolism*; D001343:Autophagy; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D066263:Protein Aggregation, Pathological / Q000378:metabolism; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*
chemical_list: D000682:Amyloid; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D046988:Proteasome Endopeptidase Complex