N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia

Engin, Atilla; Engin, Ayse Basak

doi:10.1007/978-3-030-49844-3_10

Atilla Engin⁸ &
Ayse Basak Engin⁹

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1275))

1604 Accesses
8 Citations

Abstract

Although stroke is very often the cause of death worldwide, the burden of ischemic and hemorrhagic stroke varies between regions and over time regarding differences in prognosis, prevalence of risk factors, and treatment strategies. Excitotoxicity, oxidative stress, dysfunction of the blood-brain barrier, neuroinflammation, and lysosomal membrane permeabilization, sequentially lead to the progressive death of neurons. In this process, protein kinases-related checkpoints tightly regulate N-methyl-D-aspartate (NMDA) receptor signaling pathways. One of the major hallmarks of cerebral ischemia is excitotoxicity, characterized by overactivation of glutamate receptors leading to intracellular Ca²⁺ overload and ultimately neuronal death. Thus, reduced expression of postsynaptic density-95 protein and increased protein S-nitrosylation in neurons is responsible for neuronal vulnerability in cerebral ischemia. In this chapter death-associated protein kinases, cyclin-dependent kinase 5, endoplasmic reticulum stress-induced protein kinases, hyperhomocysteinemia-related NMDA receptor overactivation, ephrin-B-dependent amplification of NMDA-evoked neuronal excitotoxicity and lysosomocentric hypothesis have been discussed.

Consequently, ample evidences have demonstrated that enhancing extrasynaptic NMDA receptor activity triggers cell death after stroke. In this context, considering the dual roles of NMDA receptors in both promoting neuronal survival and mediating neuronal damage, selective augmentation of NR2A-containing NMDA receptor activation in the presence of NR2B antagonist may constitute a promising therapy for stroke.

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Department of General Surgery, Faculty of Medicine, Gazi University, Ankara, Turkey
Atilla Engin
Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
Ayse Basak Engin

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Department of Toxicology, Faculty of Pharmacy, Gazi University, Ankara, Turkey
Ayse Basak Engin
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Atilla Engin

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Engin, A., Engin, A.B. (2021). N-Methyl-D-Aspartate Receptor Signaling-Protein Kinases Crosstalk in Cerebral Ischemia. In: Engin, A.B., Engin, A. (eds) Protein Kinase-mediated Decisions Between Life and Death. Advances in Experimental Medicine and Biology, vol 1275. Springer, Cham. https://doi.org/10.1007/978-3-030-49844-3_10

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Published: 05 February 2021
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