Nejvíce citovaný článek - PubMed ID 33669406
Allosteric Modulation of GPCRs of Class A by Cholesterol
Muscarinic acetylcholine receptors expressed in the central nervous system mediate various functions, including cognition, memory, or reward. Therefore, muscarinic receptors represent potential pharmacological targets for various diseases and conditions, such as Alzheimer's disease, schizophrenia, addiction, epilepsy, or depression. Muscarinic receptors are allosterically modulated by neurosteroids and steroid hormones at physiologically relevant concentrations. In this review, we focus on the modulation of muscarinic receptors by neurosteroids and steroid hormones in the context of diseases and disorders of the central nervous system. Further, we propose the potential use of neuroactive steroids in the development of pharmacotherapeutics for these diseases and conditions.
- Klíčová slova
- Alzheimer’s disease, Parkinson’s disease, cholesterol, depression, muscarinic receptors, neuroactive steroids, neurosteroids, schizophrenia, substance abuse,
- MeSH
- centrální nervový systém MeSH
- cholinergní látky MeSH
- hormony MeSH
- neurosteroidy * farmakologie MeSH
- receptory muskarinové MeSH
- steroidy farmakologie fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cholinergní látky MeSH
- hormony MeSH
- neurosteroidy * MeSH
- receptory muskarinové MeSH
- steroidy MeSH
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.
- Klíčová slova
- allosteric modulation, cholesterol, muscarinic receptors, neuroactive steroids, neurosteroids,
- MeSH
- cholesterol MeSH
- hormony metabolismus MeSH
- neurosteroidy * farmakologie MeSH
- receptory muskarinové MeSH
- steroidy farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cholesterol MeSH
- hormony MeSH
- neurosteroidy * MeSH
- receptory muskarinové MeSH
- steroidy MeSH