8.C.2 The Talatisamine (Talatisamine) Family 

Loss of cytosolic K⁺ through up-regulated delayed rectifier K⁺ channels plays a protective role against beta-amyloid (Aβ) induced neurotoxicity. Potent K⁺ channel blockers, specific for I(K) channels, are candidates for Alzheimer's disease (AD) treatment. Talatisamine is a I(K) channel blocker. Wang et al. (2012) examined the neuroprotective effect of talatisamine against Aβ oligomer-induced cytotoxicity in primary cultured cortical neurons. The neurotoxicity related to K⁺ loss caused by Aβ40 oligomers included enhanced I(K) density, increased cell membrane permeability, reduced cell viability, and an impaired mitochondrial transmembrane potential. Decreased Bcl-2 and increased Bax levels, activation of Caspase-3 and Caspase-9 were also observed after Aβ40 oligomer incubation. Talatisamine (120μM) inhibited the enhanced I(K) caused by Aβ40 oligomers, attenuated cytotoxicity of Aβ oligomers by restoring cell viability and suppresed K⁺-loss-related apoptotic responses (Wang et al., 2012).