| Autor: |
Menzikov SA; Institute of General Pathology and Pathophysiology, Moscow, Russia., Zaichenko DM; Institute of General Pathology and Pathophysiology, Moscow, Russia., Moskovtsev AA; Institute of General Pathology and Pathophysiology, Moscow, Russia., Morozov SG; Institute of General Pathology and Pathophysiology, Moscow, Russia., Kubatiev AA; Institute of General Pathology and Pathophysiology, Moscow, Russia. |
| Jazyk: |
angličtina |
| Zdroj: |
Frontiers in pharmacology [Front Pharmacol] 2024 Jan 18; Vol. 15, pp. 1272534. Date of Electronic Publication: 2024 Jan 18 (Print Publication: 2024). |
| DOI: |
10.3389/fphar.2024.1272534 |
| Abstrakt: |
γ-Aminobutyric acid type A receptors (GABA A Rs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which are widespread throughout the invertebrate and vertebrate central nervous system. GABA A Rs are engaged in short-term changes of the neuronal concentrations of chloride (Cl - ) and bicarbonate (HCO 3 - ) ions by their passive permeability through the ion channel pore. GABA A Rs are regulated by various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols. The wide chemical and structural variability of phenols suggest similar and different binding sites on GABA A Rs, allowing them to manifest themselves as activators, inhibitors, or allosteric ligands of GABA A R function. Interest in phenols is associated with their great potential for GABA A R modulation, but also with their subsequent negative or positive role in neurological and psychiatric disorders. This review focuses on the GABAergic deficit hypotheses during neurological and psychiatric disorders induced by various phenols. We summarize the structure-activity relationship of general phenol groups concerning their differential roles in the manifestation of neuropsychiatric symptoms. We describe and analyze the role of GABA A R subunits in manifesting various neuropathologies and the molecular mechanisms underlying their modulation by phenols. Finally, we discuss how phenol drugs can modulate GABA A R activity via desensitization and resensitization. We also demonstrate a novel pharmacological approach to treat neuropsychiatric disorders via regulation of receptor phosphorylation/dephosphorylation.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Menzikov, Zaichenko, Moskovtsev, Morozov and Kubatiev.) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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