| Summary: | 碩士 === 國立陽明大學 === 生物藥學研究所 === 103 === Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by dementia and memory loss for which no cure or effective prevention is currently available. Amyloid β protein (Aβ) is the major protein component of senile plaque, which is a hallmark of AD and has been suggested to play an important role in the pathogenesis of AD. Many natural polyphenolic compounds possess neuroprotective activity by targeting specific pathways in amyloid β protein-induced toxicity such as anti-oxidants, blockers of calcium channels, growth factors, caspase inhibitors, and flavonoids. In our previous study, tournefolic acid B (TAB) showed that it is a potent polyphenol against Aβ-induced neurotoxicity. Besides, we also focus on some potent compounds containing caffeic acid moiety, such as curcumin and salvianolic acid F (Sal F). Base on the structures of TAB, Sal F or curcumin, a series of derivatives have been newly synthesized. Therefore, we explore the neuroprotective effects of these synthetic derivatives of natural polyphenols on Aβ-induced neurotoxicity and excitotoxicity. On the one hand, we treated neurons at 6 days in vitro (DIV) with 10 μM Aβ for 48 hr and used as a cell model of Aβ-induced neurotoxicity. Moreover, we treated 9 DIV neurons with 30 μM glutamate and used as cell model of excitotoxicity. Our results showed that several compounds derived from P7C3 and Sal F are potent on protecting neurons against Aβ-mediated toxicity. Moreover, among the potent Sal F derivatives, compounds 8-56, 8-60, 8-61 were also found to be potent on protecting neurons against excitotoxicity. We also speculate that the common structure backbone (trihydroxyl group) of compound 8-56, 8-60 and 8-61, 8-68 can be a critical structure for the neuroprotective activities against Aβ-induced toxicity. Another common structure backbone (ethyl propanoate group) of compound 8-56, 8-60 and 8-61 may be a critical structure for the neuroprotective activities against glutamate-induced toxicity, and more potent candidates can be derived from these compounds.
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