Background: Alzheimer’s disease (AD) pathogenesis is primarily hallmarked by the production
and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative
disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective
therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production,
toxicity and removal of Aβ are being attempted worldwide. Prime need is to design inhibitors
which can slow down the Aβ 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 Aβ levels in AD mouse models. Administration of bexarotene
facilitates intracellular Aβ 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 Aβ 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 Aβ peptide to be crucial for
the interaction with bexarotene.
Conclusion: We speculate that direct binding of bexarotene to free Aβ peptide may lessen the concentration
of free Aβ 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