title: Protein damage, repair and proteolysis.
abstract: Proteins are continuously affected by various intrinsic and extrinsic factors. Damaged proteins influence several intracellular pathways and result in different disorders and diseases. Aggregation of damaged proteins depends on the balance between their generation and their reversal or elimination by protein repair systems and degradation, respectively. With regard to protein repair, only few repair mechanisms have been evidenced including the reduction of methionine sulfoxide residues by the methionine sulfoxide reductases, the conversion of isoaspartyl residues to L-aspartate by L-isoaspartate methyl transferase and deglycation by phosphorylation of protein-bound fructosamine by fructosamine-3-kinase. Protein degradation is orchestrated by two major proteolytic systems, namely the lysosome and the proteasome. Alteration of the function for both systems has been involved in all aspects of cellular metabolic networks linked to either normal or pathological processes. Given the importance of protein repair and degradation, great effort has recently been made regarding the modulation of these systems in various physiological conditions such as aging, as well as in diseases. Genetic modulation has produced promising results in the area of protein repair enzymes but there are not yet any identified potent inhibitors, and, to our knowledge, only one activating compound has been reported so far. In contrast, different drugs as well as natural compounds that interfere with proteolysis have been identified and/or developed resulting in homeostatic maintenance and/or the delay of disease progression.
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Helenic Research Foundation, 48 Vas. Constantinou Ave., 116 35 Athens, Greece. Electronic address: nikichon@eie.gr.
authors.forename: Niki
authors.initials: N
authors.lastname: Chondrogianni
authors.affiliation: Laboratoire de Biologie Cellulaire du Vieillissement, UR4-UPMC, IFR 83, Université Pierre et Marie Curie-Paris 6, 4 Place Jussieu, 75005 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petropoulos
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller University, Dornburger Straße 24, 07743 Jena, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Grimm
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Helenic Research Foundation, 48 Vas. Constantinou Ave., 116 35 Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Georgila
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Genetic and Metabolic Diseases Research Center (GEMHAM), Marmara University, Haydarpasa, Istanbul, Turkey.
authors.forename: Betul
authors.initials: B
authors.lastname: Catalgol
authors.affiliation: Laboratoire de Biologie Cellulaire du Vieillissement, UR4-UPMC, IFR 83, Université Pierre et Marie Curie-Paris 6, 4 Place Jussieu, 75005 Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.affiliation: Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller University, Dornburger Straße 24, 07743 Jena, Germany.
authors.forename: Tilman
authors.initials: T
authors.lastname: Grune
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Helenic Research Foundation, 48 Vas. Constantinou Ave., 116 35 Athens, Greece. Electronic address: sgonos@eie.gr.
authors.forename: Efstathios S
authors.initials: ES
authors.lastname: Gonos
mesh_terms: D001343:Autophagy; D015870:Gene Expression; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D046188:Protein Modification, Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D011506:Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D017853:Phosphotransferases (Alcohol Group Acceptor); C414347:fructosamine-3-kinase; D046988:Proteasome Endopeptidase Complex
keywords: 4-hydroxynonenal; AD; AGEs; Aging; Alzheimer’s disease; C-L; CT-L; FNK; HD; HNE; Huntington’s disease; IIS; Ins/IGF-1; Insulin/Insulin Growth Factor; Insulin/Insulin Growth Factor-1 signaling pathway; Lon protease; Lysosome; MDA; MMP; Methionine sulphoxide reductase; Msr; PD; PGPH; PIMT; Parkinson’s disease; Protein modification; RNS; ROS; Reactive oxygen species; T-L; TIMP; UPS; Ubiquitin-proteasome system; advanced glycation end products; caspase-like activity; chymotrypsin-like activity; fructosamine-3-kinase; malondialdehyde; matrix metalloproteinase; methionine sulfoxide reductase; peptidylglutamylpeptide hydrolyzing activity (or); protein L-isoaspartate methyl transferase; reactive nitrogen species; tissue inhibitor of metalloproteinase; trypsin-like activity; ubiquitin-proteasome system