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Imidazole improves cognition and balances Alzheimer's‐like intracellular calcium homeostasis in transgenic Drosophila model
Author(s) -
Li Min,
Zhang Wanrong,
Wang Wei,
He Qing,
Yin Mengmei,
Qin Xue,
Zhang Tongyu,
Wu Ting
Publication year - 2018
Publication title -
neurourology and urodynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 90
eISSN - 1520-6777
pISSN - 0733-2467
DOI - 10.1002/nau.23448
Subject(s) - imidazole , transgene , calcium in biology , microbiology and biotechnology , calcium channel , calcium , neurotoxicity , intracellular , biophysics , neuroscience , medicine , biochemistry , chemistry , biology , toxicity , gene
Aims 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 His 13 –His 14 diad. Imidazole especially the imidazole ring was supposed binding to the side chains of Aβ peptides. Methods 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. Results 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. Conclusions Furthermore, freshly prepared oligomeric Aβ42 peptide ascended primary pupal neuronal calcium concentration and this phenomenon was alleviated by Imidazole and Zn 2+ .