%A NIE Hui-Zhen, WANG Ze-Jian, ZHAO Wen-Juan, LU Jin-Miao, ZHANG Can, LUO Qing-He, WANG Yu-Liang, GAO Xiang, YIN Ming %T Effects of nicotine analog ZY-1 on β-amyloid production and learning and memory in transgenic Alzheimer disease mice %0 Journal Article %D 2011 %J ACTA NEUROPHARMACOLOGICA %R %P 26-31 %V 1 %N 1 %U {http://actanp.hebeinu.edu.cn/CN/abstract/article_6.shtml} %8 2011-02-26 %X
Objective:To observe the effects of ZY-1, a nicotine analogue, on in vitro receptor binding and β-amyloid (Aβ) production and in vivo transgenic Alzheimer’s disease mice.
Methods:Receptor binding assay was carried out in SH-EP1-α4β2 nAChR cell line highly expressing α4β2 nAChR; Western blotting was used to detect the effects of ZY-1 on amyloid protein production in the SH-EP1-α4β2 nAChR cell line transfected with APP695 plasmid; and effects of ZY-1 on learning and memory were measured in B6C3-Tg（APPswe, PSEN1dE9）85Dbo/J mice.
Results:1. Receptor binding assay showed that Ki is 21.5 n mol•L-1, suggesting specific binding of ZY-1 to α4β2 nAChR; 2. ZY-1(1 μmol•L-1) reduced intracellular production of Aβ; 3. Middle (0.50 mg•kg-1) and high dose (0.75 mg•kg-1) of ZY-1 improved learning and memory of transgenic mice in Morris water maze and platform test.
Conclusion:ZY-1 might be of potential to be an AD therapeutic agent, but the druggability remains to be further confirmed.