Imidazole improves cognition and balances Alzheimer's-like intracellular calcium homeostasis in transgenic Drosophila model.

Abstract

The characteristic of Alzheimer's disease (AD) is the accumulation and aggregation of amyloid-β (Aβ). So far, we already know that the dysregulation of intracellular calcium homeostasis is considered to be associated with Aβ neurotoxicity. Meantime, we also found that the channels formed by Aβ are electronegative as calcium channels. Base on this hypothesis, the formation of Aβ channels will provide us with a new therapeutic direction for AD. Aβ channel hypothesis is proposed that the axis of Aβ channel's pore was encompasses by the His13 -His14 diad. Imidazole especially the imidazole ring was supposed binding to the side chains of Aβ peptides. In our study, we adopted Gal4/UAS system to establish transgenic drosophila model which lay a good foundation to explore the imidazole's function and mechanism of action. The results suggested that Imidazole could not only improve the cognition of Aβ42-expressing flies, but also decreases p-JNK activation in whole brain of Aβ42-expressing flies. Furthermore, freshly prepared oligomeric Aβ42 peptide ascended primary pupal neuronal calcium concentration and this phenomenon was alleviated by Imidazole and Zn2+ .