Curcumin/Melatonin Hybrid 5-(4-Hydroxy-phenyl)-3-oxo-pentanoic Acid [2-(5-Methoxy-1H-indol-3-yl)-ethyl]-amide Ameliorates AD-Like Pathology in the APP/PS1 Mouse Model

详细信息    查看全文

• 作者：Gorka Gerenu ; Kai Liu ; Jeremy E. Chojnacki ; John M. Saathoff ; Pablo Mart铆nez-Mart铆n ; George Perry ; Xiongwei Zhu ; Hyoung-gon Lee ; Shijun Zhang
• 刊名：ACS Chemical Neuroscience
• 出版年：2015
• 出版时间：August 19, 2015
• 年：2015
• 卷：6
• 期：8
• 页码：1393-1399
• 全文大小：453K
• ISSN：1948-7193

文摘

In our efforts to develop hybrid compounds of curcumin and melatonin as potential disease-modifying agents for Alzheimer鈥檚 disease (AD), a potent lead hybrid compound, Z-CM-I-1, has been recently identified and biologically characterized in vitro. In this work, we report the in vivo effects of Z-CM-I-1 on AD pathologies in an APP/PS1 transgenic AD model. Our studies demonstrated that Z-CM-I-1 significantly decreased the accumulation of A尾 in the hippocampus and cortex regions of the brain and reduced inflammatory responses and oxidative stress after treatment for 12 weeks at 50 mg/kg per dose via oral administration. Furthermore, Z-CM-I-1 significantly improved synaptic dysfunction evidenced by the increased expression of synaptic marker proteins, PSD95 and synaptophysin, indicating its protective effects on synaptic degeneration. Lastly, we demonstrated that Z-CM-I-1 significantly increased the expression level of complexes I, II, and IV of the mitochondria electron transport chain in the brain tissue of APP/PS1 mice. Collectively, these results clearly suggest that Z-CM-I-1 is orally available and exhibits multifunctional properties in vivo on AD pathologies, thus strongly encouraging further development of this lead compound as a potential disease-modifying agent for AD patients.