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https://hdl.handle.net/10316/111942
Title: | Molecular mechanisms of ischemia and glutamate excitotoxicity | Authors: | Neves, Diogo Salazar, Ivan L. Almeida, Ramiro D. Silva, Raquel M. |
Keywords: | Ischemia; Excitotoxicity; Glutamate; Glutamate receptors; NAD | Issue Date: | 1-Sep-2023 | Publisher: | Elsevier | Project: | This work was supported by FEDER (Programa Operacional Factores de Competitividade – COMPETE) and by FCT (Fundaç˜ao para a Ciˆencia e Tecnologia), within the grant SFRH/BD/129409/2017 to DN, and the projects UIDB/04501/2020 (POCI-01-0145-FEDER-007628) and UIDP/ 04501/2020 to iBiMED and UIDB/04279/2020 to CIIS. Thanks are due to FCT/MCTES and UCP for the CEEC institutional funding of RMS (CEECINST/00137/2018/CP1520/CT0012) | Serial title, monograph or event: | Life Sciences | Volume: | 328 | Abstract: | Excitotoxicity 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. | URI: | https://hdl.handle.net/10316/111942 | ISSN: | 00243205 | DOI: | 10.1016/j.lfs.2023.121814 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Molecular mechanisms of ischemia and glutamate excitotoxicity.pdf | 3.15 MB | Adobe PDF | View/Open |
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