Kim, Eun-A Cho, Chang Hun Hahn, Hoh-Gyu Choi, Soo Young Cho, Sung-Woo 2024-01-20T08:34:54Z 2024-01-20T08:34:54Z 2021-09-02 2014-10 0272-4340 https://pubs.kist.re.kr/handle/201004/126290 Aggregated beta-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 (A beta(25-35))-induced primary cortical neuronal cell neurotoxicity. Treatment with KHG26377 attenuated the A beta(25-35)-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 A beta(25-35) exposure; however, KHG26377 treatment reversed these changes in a concentration-dependent manner. In addition, KHG26377 significantly suppressed A beta(25-35)-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 A beta toxicity was also mediated by suppressing the expression of glycogen synthase kinase-3 beta, increasing the levels of beta-catenin, and reducing the levels of phosphorylated tau. Our findings suggest that KHG26377 may modulate the neurotoxic effects of beta-amyloid and provide a rationale for treatment of AD. English SPRINGER/PLENUM PUBLISHERS NF-KAPPA-B OXIDATIVE MODIFICATION INTRACELLULAR CALCIUM INDUCED NEUROTOXICITY LIPID-PEROXIDATION ALZHEIMERS DISEASE KINASE HOMEOSTASIS PATHWAY 2-Cyclopropylimino-3-methyl-1,3-thiazoline Hydrochloride Protects Against Beta-amyloid-induced Activation of the Apoptotic Cascade in Cultured Cortical Neurons Article 10.1007/s10571-014-0080-7 1 CELLULAR AND MOLECULAR NEUROBIOLOGY, v.34, no.7, pp.963 - 972 CELLULAR AND MOLECULAR NEUROBIOLOGY 34 7 963 972 scie scopus 000342146600003 2-s2.0-84912564744 Cell Biology Neurosciences Cell Biology Neurosciences & Neurology Article NF-KAPPA-B OXIDATIVE MODIFICATION INTRACELLULAR CALCIUM INDUCED NEUROTOXICITY LIPID-PEROXIDATION ALZHEIMERS DISEASE KINASE HOMEOSTASIS PATHWAY Alzheimer&apos s disease Beta-amyloid Thiazole derivative MAP kinase Nuclear factor kappa B Tau