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- W4362692017 abstract "Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα) is a major contributor to physiological and pathological glutamate-mediated Ca2+ signals, and its involvement in various critical cellular pathways demands specific pharmacological strategies. We recently presented γ-hydroxybutyrate (GHB) ligands as the first small molecules selectively targeting and stabilizing the CaMKIIα hub domain. Here, we report that the cyclic GHB analogue 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA), improves sensorimotor function after experimental stroke in mice when administered at a clinically relevant time and in combination with alteplase. Further, we observed improved hippocampal neuronal activity and working memory after stroke. On the biochemical level, we observed that hub modulation by HOCPCA results in differential effects on distinct CaMKII pools, ultimately alleviating aberrant CaMKII signalling after cerebral ischemia. As such, HOCPCA normalised cytosolic Thr286 autophosphorylation after ischemia in mice and downregulated ischemia-specific expression of a constitutively active CaMKII kinase proteolytic fragment. Previous studies suggest holoenzyme stabilisation as a potential mechanism, yet a causal link to in vivo findings requires further studies. Similarly, HOCPCA's effects on dampening inflammatory changes require further investigation as an underlying protective mechanism. HOCPCA's selectivity and absence of effects on physiological CaMKII signalling highlight pharmacological modulation of the CaMKIIα hub domain as an attractive neuroprotective strategy." @default.
- W4362692017 created "2023-04-09" @default.
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- W4362692017 date "2023-04-07" @default.
- W4362692017 modified "2023-09-27" @default.
- W4362692017 title "The GHB analogue HOCPCA improves deficits in cognition and sensorimotor function after MCAO via CaMKIIα" @default.
- W4362692017 cites W1125777540 @default.
- W4362692017 cites W1502737496 @default.
- W4362692017 cites W1531732067 @default.
- W4362692017 cites W1931197714 @default.
- W4362692017 cites W1966014546 @default.
- W4362692017 cites W1973728299 @default.
- W4362692017 cites W1978356252 @default.
- W4362692017 cites W1979586675 @default.
- W4362692017 cites W1990999165 @default.
- W4362692017 cites W1992755028 @default.
- W4362692017 cites W1999235115 @default.
- W4362692017 cites W2003242423 @default.
- W4362692017 cites W2006786639 @default.
- W4362692017 cites W2006957980 @default.
- W4362692017 cites W2007393704 @default.
- W4362692017 cites W2009703235 @default.
- W4362692017 cites W2012014599 @default.
- W4362692017 cites W2012442696 @default.
- W4362692017 cites W2020953936 @default.
- W4362692017 cites W2025080281 @default.
- W4362692017 cites W2026602510 @default.
- W4362692017 cites W2026999094 @default.
- W4362692017 cites W2028360365 @default.
- W4362692017 cites W2030179515 @default.
- W4362692017 cites W2038636807 @default.
- W4362692017 cites W2041173396 @default.
- W4362692017 cites W2049925123 @default.
- W4362692017 cites W2052322593 @default.
- W4362692017 cites W2068704377 @default.
- W4362692017 cites W2069791066 @default.
- W4362692017 cites W2070375966 @default.
- W4362692017 cites W2076008680 @default.
- W4362692017 cites W2076575902 @default.
- W4362692017 cites W2078074974 @default.
- W4362692017 cites W2084412270 @default.
- W4362692017 cites W2086121847 @default.
- W4362692017 cites W2086164892 @default.
- W4362692017 cites W2091159900 @default.
- W4362692017 cites W2094501373 @default.
- W4362692017 cites W2097117220 @default.
- W4362692017 cites W2098674708 @default.
- W4362692017 cites W2105661186 @default.
- W4362692017 cites W2112646710 @default.
- W4362692017 cites W2113545093 @default.
- W4362692017 cites W2127366468 @default.
- W4362692017 cites W2130685693 @default.
- W4362692017 cites W2130929362 @default.
- W4362692017 cites W2135011583 @default.
- W4362692017 cites W2135285893 @default.
- W4362692017 cites W2139148538 @default.
- W4362692017 cites W2160560939 @default.
- W4362692017 cites W2167036087 @default.
- W4362692017 cites W2172001944 @default.
- W4362692017 cites W2313905667 @default.
- W4362692017 cites W2568954699 @default.
- W4362692017 cites W2568963554 @default.
- W4362692017 cites W2582319825 @default.
- W4362692017 cites W2583243478 @default.
- W4362692017 cites W2613135848 @default.
- W4362692017 cites W2613217394 @default.
- W4362692017 cites W2755583917 @default.
- W4362692017 cites W2824351696 @default.
- W4362692017 cites W2914786206 @default.
- W4362692017 cites W2919400740 @default.
- W4362692017 cites W2922230196 @default.
- W4362692017 cites W2943914132 @default.
- W4362692017 cites W2959898561 @default.
- W4362692017 cites W2965805866 @default.
- W4362692017 cites W2972782205 @default.
- W4362692017 cites W2973156172 @default.
- W4362692017 cites W2999727091 @default.
- W4362692017 cites W3005217270 @default.
- W4362692017 cites W3007594181 @default.
- W4362692017 cites W3012189330 @default.
- W4362692017 cites W3034778884 @default.
- W4362692017 cites W3044359165 @default.
- W4362692017 cites W3086248643 @default.
- W4362692017 cites W3155432123 @default.