title: Protein carbonylation, cellular dysfunction, and disease progression.
abstract: Carbonylation of proteins is an irreversible oxidative damage, often leading to a loss of protein function, which is considered a widespread indicator of severe oxidative damage and disease-derived protein dysfunction. Whereas moderately carbonylated proteins are degraded by the proteasomal system, heavily carbonylated proteins tend to form high-molecular-weight aggregates that are resistant to degradation and accumulate as damaged or unfolded proteins. Such aggregates of carbonylated proteins can inhibit proteasome activity. Alarge number of neurodegenerative diseases are directly associated with the accumulation of proteolysis-resistant aggregates of carbonylated proteins in tissues. Identification of specific carbonylated protein(s) functionally impaired and development of selective carbonyl blockers should lead to the definitive assessment of the causative, correlative or consequential role of protein carbonylation in disease onset and/or progression, possibly providing new therapeutic approaches.
authors.affiliation: Department of Biology, University of Milan, Italy. quack@unimi.it
authors.forename: Isabella
authors.initials: I
authors.lastname: Dalle-Donne
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Aldini
authors.forename: Marina
authors.initials: M
authors.lastname: Carini
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.forename: Ranieri
authors.initials: R
authors.lastname: Rossi
authors.forename: Aldo
authors.initials: A
authors.lastname: Milzani
mesh_terms: D000818:Animals; D002477:Cells / Q000378:metabolism*; D018450:Disease Progression; D005544:Forecasting; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D050050:Protein Carbonylation; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D046988:Proteasome Endopeptidase Complex