Allosteric Modulators of Potential Targets Related to Alzheimer's Disease: a Review

ChemMedChem. 2019 Aug 20;14(16):1467-1483. doi: 10.1002/cmdc.201900299. Epub 2019 Aug 1.

Abstract

Among neurodegenerative disorders, Alzheimer's disease (AD) is the most common type of dementia, and there is an urgent need to discover new and efficacious forms of treatment for it. Pathological patterns of AD include cholinergic dysfunction, increased β-amyloid (Aβ) peptide concentration, the appearance of neurofibrillary tangles, among others, all of which are strongly associated with specific biological targets. Interactions observed between these targets and potential drug candidates in AD most often occur by competitive mechanisms driven by orthosteric ligands that sometimes result in the production of side effects. In this context, the allosteric mechanism represents a key strategy; this can be regarded as the selective modulation of such targets by allosteric modulators in an advantageous manner, as this may decrease the likelihood of side effects. The purpose of this review is to present an overview of compounds that act as allosteric modulators of the main biological targets related to AD.

Keywords: Alzheimer′s disease; allosteric modulators; allosterism; biological targets; drug design.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Allosteric Regulation / drug effects*
  • Alzheimer Disease / drug therapy*
  • Amyloid Precursor Protein Secretases / antagonists & inhibitors
  • Animals
  • Glycogen Synthase Kinase 3 beta / antagonists & inhibitors
  • Humans
  • Ligands
  • Phosphodiesterase 4 Inhibitors / therapeutic use*
  • Receptors, Cell Surface / agonists*
  • Receptors, Cell Surface / antagonists & inhibitors*

Substances

  • Ligands
  • Phosphodiesterase 4 Inhibitors
  • Receptors, Cell Surface
  • Glycogen Synthase Kinase 3 beta
  • Amyloid Precursor Protein Secretases