Molecular mechanisms of ischemia and glutamate excitotoxicity.

Autor: Neves D; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal., Salazar IL; Multidisciplinary Institute of Ageing, MIA - Portugal, University of Coimbra, Coimbra, Portugal., Almeida RD; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. Electronic address: ramirodalmeida@gmail.com., Silva RM; iBiMED - Institute of Biomedicine, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal; Universidade Católica Portuguesa, Faculdade de Medicina Dentária, Centro de Investigação Interdisciplinar em Saúde, Viseu, Portugal. Electronic address: rmsilva@ucp.pt.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Sep 01; Vol. 328, pp. 121814. Date of Electronic Publication: 2023 May 24.
DOI: 10.1016/j.lfs.2023.121814
Abstrakt: 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 (Ca 2+ ) 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.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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