Bivalent Ligand Containing Curcumin and Cholesterol as a Fluorescence Probe for A尾 Plaques in Alzheimer鈥檚 Disease
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- 作者：Kai Liu ; Tai L. Guo ; Jeremy Chojnacki ; Hyoung-Gon Lee ; Xinglong Wang ; Sandra L. Siedlak ; Wei Rao ; Xiongwei Zhu ; Shijun Zhang
- 刊名：ACS Chemical Neuroscience
- 出版年：2012
- 出版时间：February 15, 2012
- 年：2012
- 卷：3
- 期：2
- 页码：141-146
- 全文大小：391K
- 年卷期：v.3,no.2(February 15, 2012)
- ISSN：1948-7193
文摘
A recently developed bivalent ligand BMAOI 14 (7) has been evaluated for its ability to label and detect aggregated 尾-amyloid (A尾) peptide as a fluorescent probe. This probe contains curcumin as the A尾 recognition moiety and cholesterol as an anchor to the neuronal cell membrane鈥搇ipid rafts. The results demonstrate that 7 binds to the monomers, oligomers, and fibrils of A尾42 with low micromolar to submicromolar binding affinities. This chemical probe also has many of the required optical properties for use in imaging and can rapidly cross the blood鈥揵rain barrier in vivo. Furthermore, 7 specifically binds to A尾 plaques in both Alzheimer's disease human patients and A尾 precursor protein transgenic mouse brain tissues. Collectively, these results suggest that 7 is a strong candidate as an A尾 imaging agent and encourage further optimization of 7 as a new lead for the development of the next generation of A尾 imaging probes.