Putting the Puzzle Together To Get the Whole Picture: Molecular Basis of the Affinity of Two Steroid Derivatives to Acetylcholinesterase.

ABSTRACT: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that has no cure because its etiology is still unknown, and its main treatment is the administration of acetylcholinesterase (AChE) inhibitors. The study of the mechanism of action of this family of compounds is critical for the design of new more potent and specific inhibitors. In this work, we study the molecular basis of an uncompetitive inhibitor (compound 1, 2β, 3α-dihydroxy-5α-cholestan-6-one disulfate), which we have proved to be a peripheral anionic site (PAS)-binding AChE inhibitor. The pipeline designed in this work is key to the development of other PAS inhibitors that not only inhibit the esterase action of the enzyme but could also modulate the non-cholinergic functions of AChE linked to the process of

SUBMITTER: Richmond V 

PROVIDER: S-EPMC10357547 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature