Effects of nicotine analog ZY-1 on β-amyloid production and learning and memory in transgenic Alzheimer disease mice

Abstract

Abstract: 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.

Key words: Alzheimer's disease, transgenic mice, receptor binding assay, nicotinic acetylcholine receptor

NIE Hui-Zhen, WANG Ze-Jian, ZHAO Wen-Juan, LU Jin-Miao, ZHANG Can, LUO Qing-He, WANG Yu-Liang, GAO Xiang, YIN Ming. Effects of nicotine analog ZY-1 on β-amyloid production and learning and memory in transgenic Alzheimer disease mice[J]. Acta Neuropharmacologica, 2011, 1(1): 26-31.

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