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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Exhibition Hall 2 |
| Time |
4월 18일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-403 |
| Subject |
Neuroprotective Effects of Nrf2 Activator via Inhibition of Protein-protein Interaction in a Mouse Model of Parkinson’s Disease |
| Authors |
Siwon Kim, Haeun Lee, Hyeon Jeong Kim, Boko Jang, Jaeick Lee1, Sang Min Lim, Ae Nim Pae*, Ki Duk Park*
Convergence Research Center for DTC, Korea Institute of Science and Technology, Korea
1Doping Control Center, Korea Institute of Science and Technology, Korea
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| Abstract |
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by abnormal movement, including slowed movements, shuffling gait, lack of balance, and tremor. Oxidative stress has been shown to play a critical role in dopaminergic neuronal cell death in PD. The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) signaling pathway provides the main defense system against oxidative stress by inducing the expression of antioxidant enzyme genes. Direct interference in the Keap1-Nrf2 protein-protein interaction (PPI) has emerged as an effective strategy for Nrf2 activation. Therefore, we searched for small-molecule PPI inhibitors that can act as Nrf2 activators by using a virtual screening approach and identified a potent Nrf2 activator, KKPA4026. KKPA4026 was confirmed to induce the expression of the Nrf2-dependent antioxidant enzymes heme oxygenase-1, glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase regulatory subunit, and NAD(P)H:quinone oxidoreductase 1 in BV-2 cells. In an MPTP-induced mouse model of PD, KKPA4026 effectively attenuated PD-associated behavioral deficits and protected dopaminergic neurons. |
| E-mail |
H15512@kist.re.kr |
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123rd General Meeting of the KCS