CaMKIIα as a Promising Drug Target for Ischemic Grey Matter

Nane Griem-Krey, Andrew N. Clarkson, Petrine Wellendorph*

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftReviewForskningpeer review

3 Citationer (Scopus)
23 Downloads (Pure)

Abstract

Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a major mediator of Ca2+-dependent signaling pathways in various cell types throughout the body. Its neuronal isoform CaMKIIα (alpha) centrally integrates physiological but also pathological glutamate signals directly downstream of glutamate receptors and has thus emerged as a target for ischemic stroke. Previous studies provided evidence for the involvement of CaMKII activity in ischemic cell death by showing that CaMKII inhibition affords substantial neuroprotection. However, broad inhibition of this central kinase is challenging because various essential physiological processes like synaptic plasticity rely on intact CaMKII regulation. Thus, specific strategies for targeting CaMKII after ischemia are warranted which would ideally only interfere with pathological activity of CaMKII. This review highlights recent advances in the understanding of how ischemia affects CaMKII and how pathospecific pharmacological targeting of CaMKII signaling could be achieved. Specifically, we discuss direct targeting of CaMKII kinase activity with peptide inhibitors versus indirect targeting of the association (hub) domain of CaMKIIα with analogues of γ-hydroxybutyrate (GHB) as a potential way to achieve more specific pharmacological modulation of CaMKII activity after ischemia.

OriginalsprogEngelsk
Artikelnummer1639
TidsskriftBrain Sciences
Vol/bind12
Udgave nummer12
Antal sider21
ISSN2076-3425
DOI
StatusUdgivet - 2022

Bibliografisk note

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© 2022 by the authors.

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