The Regulation of Astrocytic Glutamate Transporters in Health and Neurodegenerative Diseases.
Int J Mol Sci
; 21(24)2020 Dec 17.
Article
em En
| MEDLINE
| ID: mdl-33348528
ABSTRACT
The astrocytic glutamate transporters excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2) play a key role in nervous system function to maintain extracellular glutamate levels at low levels. In physiology, this is essential for the rapid uptake of synaptically released glutamate, maintaining the temporal fidelity of synaptic transmission. However, EAAT1/2 hypo-expression or hypo-function are implicated in several disorders, including epilepsy and neurodegenerative diseases, as well as being observed naturally with aging. This not only disrupts synaptic information transmission, but in extremis leads to extracellular glutamate accumulation and excitotoxicity. A key facet of EAAT1/2 expression in astrocytes is a requirement for signals from other brain cell types in order to maintain their expression. Recent evidence has shown a prominent role for contact-dependent neuron-to-astrocyte and/or endothelial cell-to-astrocyte Notch signalling for inducing and maintaining the expression of these astrocytic glutamate transporters. The relevance of this non-cell-autonomous dependence to age- and neurodegenerative disease-associated decline in astrocytic EAAT expression is discussed, plus the implications for disease progression and putative therapeutic strategies.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
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Astrócitos
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Ácido Glutâmico
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Transportador 1 de Aminoácido Excitatório
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Transportador 2 de Aminoácido Excitatório
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Reino Unido