Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/106952
Title: | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders | Authors: | Mele, Miranda Costa, Rui O. Duarte, Carlos B. |
Keywords: | GABAA receptor trafficking; epilepsy; brain ischemia; Alzheimer’s disease; Huntington’s disease; Parkinson’s disease | Issue Date: | 2019 | Publisher: | Frontiers Media S.A. | Project: | This work was financed by the European Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme under project CENTRO- 01-0145-FEDER-000008:BrainHealth 2020, and through the COMPETE 2020—Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT—Fundação para a Ciência e a Tecnologia, I.P., under projects POCI-01-0145-FEDER-007440 and CENTRO- 01-0145-FEDER-030659. FCT also supported the following individual grants: SFRH/BPD/115546/2016 (MM) and SFRH/BPD/84593/2012 (RC). | Serial title, monograph or event: | Frontiers in Cellular Neuroscience | Volume: | 13 | Abstract: | GABAA receptors (GABAAR) are the major players in fast inhibitory neurotransmission in the central nervous system (CNS). Regulation of GABAAR trafficking and the control of their surface expression play important roles in the modulation of the strength of synaptic inhibition. Different pieces of evidence show that alterations in the surface distribution of GABAAR and dysregulation of their turnover impair the activity of inhibitory synapses. A diminished efficacy of inhibitory neurotransmission affects the excitatory/inhibitory balance and is a common feature of various disorders of the CNS characterized by an increased excitability of neuronal networks. The synaptic pool of GABAAR is mainly controlled through regulation of internalization, recycling and lateral diffusion of the receptors. Under physiological condition these mechanisms are finely coordinated to define the strength of GABAergic synapses. In this review article, we focus on the alteration in GABAAR trafficking with an impact on the function of inhibitory synapses in various disorders of the CNS. In particular we discuss how similar molecular mechanisms affecting the synaptic distribution of GABAAR and consequently the excitatory/inhibitory balance may be associated with a wide diversity of pathologies of the CNS, from psychiatric disorders to acute alterations leading to neuronal death. A better understanding of the cellular and molecular mechanisms that contribute to the impairment of GABAergic neurotransmission in these disorders, in particular the alterations in GABAAR trafficking and surface distribution, may lead to the identification of new pharmacological targets and to the development of novel therapeutic strategies. | URI: | https://hdl.handle.net/10316/106952 | ISSN: | 1662-5102 | DOI: | 10.3389/fncel.2019.00077 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais IIIUC - Artigos em Revistas Internacionais FCTUC Ciências da Vida - Artigos em Revistas Internacionais |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
fncel-13-00077.pdf | 1.55 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
62
checked on Aug 5, 2024
WEB OF SCIENCETM
Citations
59
checked on Aug 2, 2024
Page view(s)
63
checked on Aug 13, 2024
Download(s)
22
checked on Aug 13, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License