Alzheimer's disease therapeutic candidate SAK3 is an enhancer of T-type calcium channels

Kohji Fukunaga, Hisanao Izumi, Yasushi Yabuki, Yasuharu Shinoda, Norifumi Shioda, Feng Han

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

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 languageEnglish
Pages (from-to)51-58
Number of pages8
JournalJournal of Pharmacological Sciences
Volume139
Issue number2
DOIs
Publication statusPublished - 2019 Feb

Keywords

  • Alzheimer's disease
  • CaMKII
  • Cognitive function
  • Proteasome activity
  • T-type Ca channel enhancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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