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Critical Reviews™ in Therapeutic Drug Carrier Systems
Fator do impacto: 2.9 FI de cinco anos: 3.72 SJR: 0.736 SNIP: 0.551 CiteScore™: 2.43

ISSN Imprimir: 0743-4863
ISSN On-line: 2162-660X

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Critical Reviews™ in Therapeutic Drug Carrier Systems

DOI: 10.1615/CritRevTherDrugCarrierSyst.v27.i2.10
pages 85-154

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

Mark A. Babizhayev
Innovative Vision Products, Inc., USA; and Moscow Helmholtz Research Institute for Eye Diseases, Moscow, Russian Federation
Dr. Babizhayev has over 15 international Patents to his name and over 100 publications issued
Yegor E. Yegorov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation

RESUMO

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 imidazolecontaining 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.