Journal
JOURNAL OF PHARMACOLOGICAL SCIENCES
Volume 139, Issue 2, Pages 51-58Publisher
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2018.11.014
Keywords
T-type Ca2+ channel enhancer; CaMKII; Proteasome activity; Alzheimer's disease; Cognitive function
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Funding
- Project of Translational and Clinical Research Core Centers from AMED
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Low-threshold Ca2+ spikes are mediated by T-type Ca2+ channels, which have electrophysiological properties of fast inactivation and slow deactivation kinetics. A low membrane potential of approximately -60 mV is sufficient to trigger channel opening. We recently introduced a novel T-type Ca2+ channel enhancer that improves cognition and inhibits amyloid beta aggregation in an Alzheimer's disease (AD) mouse model. The enhancer stimulates ACh release, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, and neurogenesis in the hippocampus. Then, we discuss how T-type Ca2+ channel enhancer improves cognition and impaired neurogenesis and how CaMKII signaling in neuro-degenerative diseases reduces amyloid beta aggregation. We provide a perspective of the potential AD therapies to target CaMKII signaling. In this context, we overview our attempts leading to the development of a T-type Ca2+ channel enhancer as cognitive enhancer, the action of which has been associated with CaMKII and presumably proteasome activity. (c) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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