Diazoxide and cyclosporin A protect primary cholinergic neurons against beta-amyloid (1-42)-induced cytotoxicity

Abstract

The present research demonstrates that activation of MitoKATP channels independently or in combination with inhibitors of the MTP can elicit a protective effect against primary cholinergic neuron cytotoxicity induced by A-beta1-42. These findings suggest new mitochondrial targets for the development of therapeutic agents against A-beta-induced cytotoxicity.

Vitamin D cell signalling in health and disease

“…4). Opening of the mitochondrial K ATP channels by diazoxide reduces ROS formation [80,81]. The resulting hyperpolarization of the mitochondrial membrane potential will reduce both mitochondrial Ca 2þ uptake and the resulting increase in ROS production and this may explain the beneficial effects of diazoxide in neurodegenerative diseases such as AD [81] and multiple sclerosis (MS) [80].…”

KATP channel block prevents proteasome inhibitor-induced apoptosis in differentiated PC12 cells

“…Diazoxide reduces cell death by ameliorating the β-amyloid peptide (A-beta1-42)-induced decrease in the expression of Bcl-2, cytochrome c release, and caspase-3 activation in rat forebrain cholinergic neurons (Zeng et al, 2013). Diazoxide inhibits rotenone-induced neuro-inflammation and neuronal cell death by suppressing microglial activation and the production of pro-inflammatory factors, such as TNF-α and prostaglandin E 2 (Zhou et al, 2008).…”

“…Activation of K ATP channels can exert neuroprotective and anti-inflammatory effects on the brain, protecting against ischemia, trauma, and neurotoxicants (Robin et al, 2011;Roseborough et al, 2006;Zhou et al, 2008). The K ATP channel opener diazoxide protects neuronal cells against amyloid β-peptide, N-methyl-D-aspartate, 1-methyl-4-phenylpyridinium and rotenone Zeng et al, 2013;Zhou et al, 2008). The cytoprotective effect of diazoxide is inhibited by the selective mitochondrial K ATP channel inhibitor 5-hydroxydecanoate and the cell surface and mitochondrial K ATP channel inhibitor glibenclamide (Kong and Ba, 2012;Watanabe et al, 2008;Zarch et al, 2009).…”

Anti-amyloidogenic Heterocyclic Peptides

“…In this context, cyclosporine was reported to protect primary cholinergic neurons against Aβ42-induced cytotoxicity [151]. Determination of cell morphology and cell viability together with expression levels of anti-apoptotic proteins revealed that cyclosporin exerts significant protective effects on the viability of cultured rat primary basal forebrain cholinergic neurons by ameliorating the decrease in Bcl-2 anti-apoptotic protein and the increase in apoptotic cytochrome c and caspase-3 activity induced by Aβ42 [151].…”