Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease

Molecules. 2018 Dec 7;23(12):3230. doi: 10.3390/molecules23123230.

Abstract

The cholinergic hypothesis has been reported first being the cause of memory dysfunction in the Alzheimer's disease. Researchers around the globe have focused their attention on understanding the mechanisms of how this complicated system contributes to processes such as learning, memory, disorientation, linguistic problems, and behavioral issues in the indicated chronic neurodegenerative disease. The present review reports recent updates in hybrid molecule design as a strategy for selectively addressing multiple target proteins involved in Alzheimer's disease (AD) and the study of their therapeutic relevance. The rationale and the design of the bifunctional compounds will be discussed in order to understand their potential as tools to investigate the role of the cholinergic system in AD.

Keywords: AChE inhibitor; Alzheimer’s disease; bitopic ligand; cholinergic system; hybrid molecules; muscarinic receptors; nicotinic receptors.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Animals
  • Cholinergic Agents / metabolism*
  • Drug Delivery Systems*
  • Humans
  • Memory
  • Receptors, Muscarinic / metabolism*
  • Receptors, Nicotinic / metabolism*

Substances

  • Cholinergic Agents
  • Receptors, Muscarinic
  • Receptors, Nicotinic