Low-threshold Ca spikes are mediated by T-type Ca 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 Ca channel enhancer that improves cognition and inhibits amyloid beta aggregation in an Alzheimer's disease (AD) mouse model. The enhancer stimulates ACh release, Ca/calmodulin-dependent protein kinase II (CaMKII) activity, and neurogenesis in the hippocampus. Then, we discuss how T-type Ca channel enhancer improves cognition and impaired neurogenesis and how CaMKII signaling in neurodegenerative 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 Ca channel enhancer as cognitive enhancer, the action of which has been associated with CaMKII and presumably proteasome activity.
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