Abstract
Background: Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (A beta) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-A beta targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of A beta are being attempted worldwide. Prime need is to design inhibitors which can slow down the A beta aggregation process in a physiological environment. Bexarotene (targretin) is the first of the U. S. Food and Drug Administration approved oral retinoid X receptors (RXR)-selective retinoids, or rexinoids. It is effectively used for the treatment of advanced, refractory cutaneous T cell lymphoma, and also reportedly reduces A beta levels in AD mouse models. Administration of bexarotene facilitates intracellular A beta clearance via RXR regulated apolipoprotein E (ApoE) production.
Objective: To the best of our knowledge, this is the first structural attempt to find binding interactions of the drug bexarotene with monomeric A beta peptide.
Method: We checked binding possibilities of bexarotene by using structural bioinformatics method.
Results: We found in our study the basic amino acids His13 and Lys 16 of A beta peptide to be crucial for the interaction with bexarotene.
Conclusion: We speculate that direct binding of bexarotene to free A beta peptide may lessen the concentration of free A beta peptides in the brain and hamper the propensity of the peptide's clumping and aggregating behavior. Further experimental validation of the results of this study would be required for its therapeutic success.