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Fundamental neurochemistry review: Glutamatergic dysfunction as a central mechanism underlying flavivirus‐induced neurological damage
Abstract The Flaviviridae family comprises positive‐sense single‐strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile v...
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Published in: | Journal of neurochemistry 2023-09, Vol.166 (6), p.915-927 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | Abstract
The
Flaviviridae
family comprises positive‐sense single‐strand RNA viruses mainly transmitted by arthropods. Many of these pathogens are especially deleterious to the nervous system, and a myriad of neurological symptoms have been associated with infections by Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) in humans. Studies suggest that viral replication in neural cells and the massive release of pro‐inflammatory mediators lead to morphological alterations of synaptic spine structure and changes in the balance of excitatory/inhibitory neurotransmitters and receptors. Glutamate is the predominant excitatory neurotransmitter in the brain, and studies propose that either enhanced release or impaired uptake of this amino acid contribute
s
to brain damage in several conditions. Here, we review existing evidence suggesting that glutamatergic dysfunction
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induced by flaviviruses is a central mechanism for neurological damage and clinical outcomes of infection. We also discuss current data suggesting that pharmacological approaches that counteract glutamatergic dysfunction show benefits in animal models of such viral diseases.
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ISSN: | 0022-3042 1471-4159 1471-4159 |
DOI: | 10.1111/jnc.15935 |