Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/50245 |
Resumo: | Copyright © 2020 Armada-Moreira, Gomes, Pina, Savchak, Gonçalves-Ribeiro, Rei, Pinto, Morais, Martins, Ribeiro, Sebastião, Crunelli and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseasesNMDA receptorsAstrocytesCalcium signalingExcitotoxicityNeurodegenerative diseasesOxidative stressCopyright © 2020 Armada-Moreira, Gomes, Pina, Savchak, Gonçalves-Ribeiro, Rei, Pinto, Morais, Martins, Ribeiro, Sebastião, Crunelli and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.This work was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/BTM-SAL/32147/2017, PD/BD/114278/2016, IMM/BI/2-2020), and by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado (UID/BIM/50005/2019). TM was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska/Curie grant agreement No. 722053.FrontiersRepositório da Universidade de LisboaArmada-Moreira, AdamGomes, Joana I.Pina, Carolina CamposSavchak, Oksana K.Gonçalves-Ribeiro, JoanaRei, NádiaPinto, SaraMorais, Tatiana P.Martins, Robertta SilvaRibeiro, FilipaSebastião, Ana MCrunelli, VincenzoVaz, Sandra H.2021-12-02T14:56:15Z20202020-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50245engFront Cell Neurosci. 2020 Apr 24;14:9010.3389/fncel.2020.000901662-5102info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:15Zoai:repositorio.ul.pt:10451/50245Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:41.366621Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| title |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| spellingShingle |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases Armada-Moreira, Adam NMDA receptors Astrocytes Calcium signaling Excitotoxicity Neurodegenerative diseases Oxidative stress |
| title_short |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| title_full |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| title_fullStr |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| title_full_unstemmed |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| title_sort |
Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases |
| author |
Armada-Moreira, Adam |
| author_facet |
Armada-Moreira, Adam Gomes, Joana I. Pina, Carolina Campos Savchak, Oksana K. Gonçalves-Ribeiro, Joana Rei, Nádia Pinto, Sara Morais, Tatiana P. Martins, Robertta Silva Ribeiro, Filipa Sebastião, Ana M Crunelli, Vincenzo Vaz, Sandra H. |
| author_role |
author |
| author2 |
Gomes, Joana I. Pina, Carolina Campos Savchak, Oksana K. Gonçalves-Ribeiro, Joana Rei, Nádia Pinto, Sara Morais, Tatiana P. Martins, Robertta Silva Ribeiro, Filipa Sebastião, Ana M Crunelli, Vincenzo Vaz, Sandra H. |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Armada-Moreira, Adam Gomes, Joana I. Pina, Carolina Campos Savchak, Oksana K. Gonçalves-Ribeiro, Joana Rei, Nádia Pinto, Sara Morais, Tatiana P. Martins, Robertta Silva Ribeiro, Filipa Sebastião, Ana M Crunelli, Vincenzo Vaz, Sandra H. |
| dc.subject.por.fl_str_mv |
NMDA receptors Astrocytes Calcium signaling Excitotoxicity Neurodegenerative diseases Oxidative stress |
| topic |
NMDA receptors Astrocytes Calcium signaling Excitotoxicity Neurodegenerative diseases Oxidative stress |
| description |
Copyright © 2020 Armada-Moreira, Gomes, Pina, Savchak, Gonçalves-Ribeiro, Rei, Pinto, Morais, Martins, Ribeiro, Sebastião, Crunelli and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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2020 |
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2020 2020-01-01T00:00:00Z 2021-12-02T14:56:15Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/50245 |
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http://hdl.handle.net/10451/50245 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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Front Cell Neurosci. 2020 Apr 24;14:90 10.3389/fncel.2020.00090 1662-5102 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Frontiers |
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Frontiers |
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