RT Journal Article
ID 00fdd1943f3a749d
A1 Babizhayev, Mark A.
A1 Yegorov, Yegor E.
T1  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
JF Critical Reviews™ in Therapeutic Drug Carrier Systems
JO CRT
YR 2010
FD 2010-05-21
VO 27
IS 2
SP 85
OP 154
K1 natural imidazole-containing peptidomimetics
K1 carcinine
K1 N-acetylcarnosine
K1 l-carnosine
K1 leucyl-histidylhydrazide
K1 chemical and pharmacological chaperones
K1 skin care
K1 photoaging
K1 cosmetic science
K1 alpha A-crystallin
K1 ophthalmic treatment
K1 age-related cataract
K1 age-related
AB The purpose of this study was to determine how the naturally occurring molecules <i>N</i>-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 <i>N</i>-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.
PB Begell House
LK https://www.dl.begellhouse.com/journals/3667c4ae6e8fd136,084c773c4be05381,00fdd1943f3a749d.html