Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders
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 evi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00077/full |
| _version_ | 1818175616392888320 |
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| author | Miranda Mele Miranda Mele Rui O. Costa Rui O. Costa Carlos B. Duarte Carlos B. Duarte |
| author_facet | Miranda Mele Miranda Mele Rui O. Costa Rui O. Costa Carlos B. Duarte Carlos B. Duarte |
| author_sort | Miranda Mele |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T20:03:08Z |
| format | Article |
| id | doaj.art-0fc23c7867a1441596d39ee226e53290 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-11T20:03:08Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-0fc23c7867a1441596d39ee226e532902022-12-22T00:52:28ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-03-011310.3389/fncel.2019.00077439774Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain DisordersMiranda Mele0Miranda Mele1Rui O. Costa2Rui O. Costa3Carlos B. Duarte4Carlos B. Duarte5CNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalInstitute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalInstitute for Interdisciplinary Research, University of Coimbra, Coimbra, PortugalCNC—Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, PortugalDepartment of Life Sciences, University of Coimbra, Coimbra, PortugalGABAA 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.https://www.frontiersin.org/article/10.3389/fncel.2019.00077/fullGABAA receptor traffickingepilepsybrain ischemiaAlzheimer’s diseaseHuntington’s diseaseParkinson’s disease |
| spellingShingle | Miranda Mele Miranda Mele Rui O. Costa Rui O. Costa Carlos B. Duarte Carlos B. Duarte Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders Frontiers in Cellular Neuroscience GABAA receptor trafficking epilepsy brain ischemia Alzheimer’s disease Huntington’s disease Parkinson’s disease |
| title | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders |
| title_full | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders |
| title_fullStr | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders |
| title_full_unstemmed | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders |
| title_short | Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders |
| title_sort | alterations in gabaa receptor trafficking and synaptic dysfunction in brain disorders |
| topic | GABAA receptor trafficking epilepsy brain ischemia Alzheimer’s disease Huntington’s disease Parkinson’s disease |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00077/full |
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