Therapeutic uses of drug-carrier systems for imidazole-containing dipeptide compounds that act as pharmacological chaperones and have significant impact on the treatment of chronic diseases associated with increased oxidative stress and the formation of advanced glycation end products.
The purpose of this study was to determine how the naturally occurring molecules N-acetylcarnosine, L-carnosine, and carcinine, which are chemical or pharmacological chaperones, affect the cells and biomolecules of patients with skin diseases, cosmetic skin lesions, or underlying clinically significant visual impairment such as age-related cataracts, age-related retinal degeneration, and ocular complications of diabetes. We evaluated and characterized the effects of cited pharmacological chaperones on enzyme activity, protein structure in tissues, and other biomarkers of diseases in skin cells and tissues or in ocular tissues (human cataractous and normal lenses) derived from ophthalmic patients or age-matched donors. The samples were used to test imidazole-containing peptidomimetic chemical/pharmacological chaperones in relation to oxidative stress induced by reaction with lipid peroxides or advanced non-enzymatic glycation processes. Chaperone function is characterized by interaction with other proteins, mediating their folding, transport, and interaction with other molecules, lipid peroxidation products, and membranes. Although these therapies remain on hold pending further investigation, we present growing evidence demonstrating the ability of N-acetylcarnosine (lubricant eye drops) or carcinine pharmacological chaperone therapy to act as novel treatments for age-related cataracts, age-related macular degeneration, and ocular complications of diabetes. Finally, we examine strategies for identifying potential chaperone compounds and for experimentally demonstrating chaperone and transglycating (de-glycation) types of activity in in vitro and in vivo models of human age-related eye diseases, such as cataracts, and advanced glycation tissue protein-engineered systems.
Babizhayev
Mark A
MA
Innovative Vision Products, Inc., USA; and Moscow Helmholtz Research Institute for Eye Diseases, Moscow, Russian Federation. markbabizhayev@yahoo.com
Yegorov
Yegor E
YE
D000375:Aging / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002336:Carnosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical; D002908:Chronic Disease; D004337:Drug Carriers; D004339:Drug Compounding; D015195:Drug Design; D005128:Eye Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship
D015415:Biomarkers; D004337:Drug Carriers; D017127:Glycation End Products, Advanced; C033681:N-acetylcarnosine; D002336:Carnosine; C015055:carcinine