Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca 2+ /CaMKII/CREB signaling pathway

Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly imp...

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Bibliographic Details
Published in:Experimental neurology 2020-05, Vol.327, p.113210
Main Authors: Chen, Chen, Xu, Di, Zhang, Zhong-Hao, Jia, Shi-Zheng, Cao, Xian-Chun, Chen, Yu-Bin, Song, Guo-Li, Wong, Man Shing, Li, Hung Wing
Format: Article
Language:English
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Summary:Accumulation of β-amyloid (Aβ) peptide and hyperphosphorylated tau in the brain is one of the pathological characteristics of Alzheimer's disease (AD) and attractive therapeutic targets in its treatment. In the present study, the cognitive ability of 4-month-old 3 × Tg-AD mice significantly improved after 40 days treatment with intraperitoneal injection of 2.25 mg/kg of SLOH, which is a multifunctional carbazole-based cyanine fluorophore. It reduced Aβ deposition, tau levels and its hyperphosphorylation by modulating AKT and promoting protein phosphatase 2A activity in the brain as well as in the primary neurons of 3 × Tg-AD mice. Moreover, SLOH attenuated synaptic deficit both in vitro and in vivo by regulating the Ca /CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.
ISSN:1090-2430