Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors.
Reactive carbonyl compounds (RCCs) formed during lipid peroxidation and sugar glycoxidation, namely Advanced lipid peroxidation end products (ALEs) and Advanced Glycation end products (AGEs), accumulate with ageing and oxidative stress-related diseases, such as atherosclerosis, diabetes or neurodegenerative diseases. RCCs induce the 'carbonyl stress' characterized by the formation of adducts and cross-links on proteins, which progressively leads to impaired protein function and damages in all tissues, and pathological consequences including cell dysfunction, inflammatory response and apoptosis. The prevention of carbonyl stress involves the use of free radical scavengers and antioxidants that prevent the generation of lipid peroxidation products, but are inefficient on pre-formed RCCs. Conversely, carbonyl scavengers prevent carbonyl stress by inhibiting the formation of protein cross-links. While a large variety of AGE inhibitors has been developed, only few carbonyl scavengers have been tested on ALE-mediated effects. This review summarizes the signalling properties of ALEs and ALE-precursors, their role in the pathogenesis of oxidative stress-associated diseases, and the different agents efficient in neutralizing ALEs effects in vitro and in vivo. The generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of carbonyl stress-associated diseases.
Negre-Salvayre
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A
INSERM U858, IFR-31 and Biochemistry Department, CHU Rangueil, University Toulouse-3, Toulouse, France. anesalv@toulouse.inserm.fr
Coatrieux
C
C
Ingueneau
C
C
Salvayre
R
R
D000375:Aging / Q000378:metabolism; D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000209:etiology; D002453:Cell Cycle / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000209:etiology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology; D019636:Neurodegenerative Diseases / Q000209:etiology; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D015398:Signal Transduction
D000447:Aldehydes; D000975:Antioxidants; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D011506:Proteins; C027576:4-hydroxy-2-nonenal