CaMKIIα as a Promising Drug Target for Ischemic Grey Matter

Your doctor should know about all this previous research. And should be initiating human testing.

The CaMKIIα hub ligand Ph-HTBA promotes neuroprotection after focal ischemic stroke by a distinct molecular interaction 2022 

GHB analogs confer neuroprotection through specific interaction with the CaMKIIα hub domain 2021 

Dihydrolipoic Acid Inhibits Lysosomal Rupture and NLRP3 Through Lysosome-Associated Membrane Protein-1/Calcium/Calmodulin-Dependent Protein Kinase II/TAK1 Pathways After Subarachnoid Hemorrhage in Rat 2018

Exploring the NCS-382 Scaffold for CaMKIIα Modulation: Synthesis, Biochemical Pharmacology, and Biophysical Characterization of Ph-HTBA as a Novel High-Affinity Brain-Penetrant Stabilizer of the CaMKIIα Hub Domain2022

 

 

The latest here: If your doctor doesn't know of all  of these you don't have a functioning stroke doctor.

CaMKIIα as a Promising Drug Target for Ischemic Grey Matter

Nane Griem-Krey 1 , Andrew N. Clarkson 2 and Petrine Wellendorph 1,*
1 Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark
2 Department of Anatomy, Brain Health Research Centre and Brain Research New Zealand,
University of Otago, Dunedin 9016, New Zealand
* Correspondence: pw@sund.ku.dk; Tel.: +45-3533-6397

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.(I call it stopping the  neuronal cascade of death.) 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.