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Molecular mechanisms of ischemia and glutamate excitotoxicity

dc.contributor.authorNeves, Diogo
dc.contributor.authorSalazar, Ivan L.
dc.contributor.authorAlmeida, Ramiro D.
dc.contributor.authorSilva, Raquel M.
dc.date.accessioned2023-06-21T16:58:06Z
dc.date.available2023-06-21T16:58:06Z
dc.date.issued2023-09-01
dc.description.abstractExcitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.g. ischemic stroke). Multiple mechanisms and pathways lead to excitotoxic cell damage including pro-death signaling cascade events downstream of glutamate receptors, calcium (Ca2+) overload, oxidative stress, mitochondrial impairment, excessive glutamate in the synaptic cleft as well as altered energy metabolism. Here, we review the current knowledge on the molecular mechanisms that underlie excitotoxicity, emphasizing the role of Nicotinamide Adenine Dinucleotide (NAD) metabolism. We also discuss novel and promising therapeutic strategies to treat excitotoxicity, highlighting recent clinical trials. Finally, we will shed light on the ongoing search for stroke biomarkers, an exciting and promising field of research, which may improve stroke diagnosis, prognosis and allow better treatment options.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1016/j.lfs.2023.121814pt_PT
dc.identifier.eid85162900224
dc.identifier.issn0024-3205
dc.identifier.pmid37236602
dc.identifier.urihttp://hdl.handle.net/10400.14/41400
dc.identifier.wos001038965000001
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectIschemiapt_PT
dc.subjectExcitotoxicitypt_PT
dc.subjectGlutamatept_PT
dc.subjectGlutamate receptorspt_PT
dc.subjectNADpt_PT
dc.titleMolecular mechanisms of ischemia and glutamate excitotoxicitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleLife Sciencespt_PT
oaire.citation.volume328
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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