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Cellular and Molecular Neurobiology

, Volume 34, Issue 7, pp 963–972 | Cite as

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

  • Eun-A Kim
  • Chang Hun Cho
  • Hoh-Gyu Hahn
  • Soo Young Choi
  • Sung-Woo Cho
Short Communication

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.

Keywords

Alzheimer’s disease Beta-amyloid Thiazole derivative MAP kinase Nuclear factor kappa B Tau 

Notes

Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A2041484), by the Korea Institute of Science and Technology Institutional Program, and by a Student Research Grant from the University of Ulsan College of Medicine, Seoul, Korea.

Conflict of interest

The authors have declared no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Eun-A Kim
    • 1
  • Chang Hun Cho
    • 1
  • Hoh-Gyu Hahn
    • 2
  • Soo Young Choi
    • 3
  • Sung-Woo Cho
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Ulsan College of MedicineSeoulKorea
  2. 2.Chemical Kinomics Research CenterKorea Institute of Science and TechnologySeoulKorea
  3. 3.Department of Biomedical Science and Research Institute of Bioscience and BiotechnologyHallym UniversityChuncheonKorea

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