2-Cyclopropylimino-3-methyl-1,3-thiazoline Hydrochloride Protects Against Beta-amyloid-induced Activation of the Apoptotic Cascade in Cultured Cortical Neurons

Title
2-Cyclopropylimino-3-methyl-1,3-thiazoline Hydrochloride Protects Against Beta-amyloid-induced Activation of the Apoptotic Cascade in Cultured Cortical Neurons
Authors
김은아조창훈한호규최수영조성우
Keywords
Alzheimer disease; beta-amyloid; Thiazole derivative; MAP kinase; protective effect of neuronal cell; Nuclear factor kappa B; Tau
Issue Date
2014-10
Publisher
Cellular and molecular neurobiology
Citation
VOL 34, NO 7, 963-972
Abstract
Aggregated β-amyloid, implicated in the pathogenesis of Alzheimer’s disease (AD), induces neurotoxicity by evoking a cascade of oxidative damage-dependent apoptosis in neurons. We investigated the molecular mechanisms underlying the protective effect of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride (KHG26377) against the beta-amyloid (Aβ25–35)-induced primary cortical neuronal cell neurotoxicity. Treatment with KHG26377 attenuated the Aβ25–35-induced apoptosis by decreasing the Bax/Bcl-2 ratio and suppressing the activation of caspase-3. A marked increase in calcium influx and in the level of reactive oxygen species together with a decrease in glutathione levels was found after Aβ25–35 exposure; however, KHG26377 treatment reversed these changes in a concentration-dependent manner. In addition, KHG26377 significantly suppressed Aβ25–35-induced toxicity concomitant with a reduction in the activation of extracellular signal-regulated kinases 1 and 2 and nuclear factor kappa B. The KHG26377-induced protection of neuronal cells against Aβ toxicity was also mediated by suppressing the expression of glycogen synthase kinase-3β, increasing the levels of β-catenin, and reducing the levels of phosphorylated tau. Our findings suggest that KHG26377 may modulate the neurotoxic effects of β-amyloid and provide a rationale for treatment of AD.
URI
http://pubs.kist.re.kr/handle/201004/48132
ISSN
02724340
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KIST Publication > Article
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