Cognitive improvement and synaptic deficit attenuation by a multifunctional carbazole-based cyanine in AD mice model through regulation of Ca2+/CaMKII/CREB signaling pathway

Chen Chen, Di Xu, Zhong Hao Zhang, Shi Zheng Jia, Xian Chun Cao, Yu Bin Chen, Guo Li Song*, Ricky M S Wong*, Hung Wing Li*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

10 Citations (Scopus)
35 Downloads (Pure)

Abstract

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 Ca2+/CaMKII/CREB signaling pathway. These findings strongly suggest that SLOH owns a high therapeutic potential to treat early onset AD.

Original languageEnglish
Article number113210
JournalExperimental Neurology
Volume327
DOIs
Publication statusPublished - May 2020

Scopus Subject Areas

  • Neurology
  • Developmental Neuroscience

User-Defined Keywords

  • Alzheimer's disease
  • Calcium pathway
  • Hyperphosphorylated tau
  • SLOH

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