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.