Abstract
Low-threshold Ca 2+ spikes are mediated by T-type Ca 2+ 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 2+ channel enhancer that improves cognition and inhibits amyloid beta aggregation in an Alzheimer's disease (AD) mouse model. The enhancer stimulates ACh release, Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) activity, and neurogenesis in the hippocampus. Then, we discuss how T-type Ca 2+ 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 2+ channel enhancer as cognitive enhancer, the action of which has been associated with CaMKII and presumably proteasome activity.
Original language | English |
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Pages (from-to) | 51-58 |
Number of pages | 8 |
Journal | Journal of Pharmacological Sciences |
Volume | 139 |
Issue number | 2 |
DOIs | |
Publication status | Published - 2019 Feb |
Keywords
- Alzheimer's disease
- CaMKII
- Cognitive function
- Proteasome activity
- T-type Ca channel enhancer
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology