Allosteric Modulation of Muscarinic Receptors by Cholesterol, Neurosteroids and Neuroactive Steroids

Int J Mol Sci. 2022 Oct 28;23(21):13075. doi: 10.3390/ijms232113075.

Abstract

Muscarinic acetylcholine receptors are membrane receptors involved in many physiological processes. Malfunction of muscarinic signaling is a cause of various internal diseases, as well as psychiatric and neurologic conditions. Cholesterol, neurosteroids, neuroactive steroids, and steroid hormones are molecules of steroid origin that, besides having well-known genomic effects, also modulate membrane proteins including muscarinic acetylcholine receptors. Here, we review current knowledge on the allosteric modulation of muscarinic receptors by these steroids. We give a perspective on the research on the non-genomic effects of steroidal compounds on muscarinic receptors and drug development, with an aim to ultimately exploit such knowledge.

Keywords: allosteric modulation; cholesterol; muscarinic receptors; neuroactive steroids; neurosteroids.

Publication types

  • Review

MeSH terms

  • Cholesterol
  • Hormones / metabolism
  • Neurosteroids* / pharmacology
  • Receptors, Muscarinic
  • Steroids / pharmacology

Substances

  • Neurosteroids
  • Hormones
  • Receptors, Muscarinic
  • Steroids
  • Cholesterol