Pharmacological activation of the Nrf2 pathway by 3H-1, 2-dithiole-3-thione is neuroprotective in a mouse model of Alzheimer disease

Yuan Bo Cui, Shan Shan Ma, Chun Yan Zhang, Dong Peng Li, Bo Yang, Peng Ju Lv, Qu Xing, Tuanjie Huang, Greta Luyuan Yang, Wei Cao, Fang Xia Guan

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Accumulating evidence suggests that oxidative stress induced by beta-amyloid (Aβ) is implicated in the pathlogical progression of Alzheimer's disease (AD). 3H-1,2-dithiole-3-thione (D3T), the simplest compound of the sulfur-containing dithiolethiones, has been proved to be a strongly active antioxidant factor by regulation of the nuclear factor E2-related factor 2 (Nrf2). Previous study reported that D3T confers protection to AD cell model in vitro, however, the neuroprotective effect of D3T in the AD mammalian model is unknown. In the present study, we aimed to evaluate the therapeutic potential of D3T in the Tg2576 AD mouse model and investigate the mechanisms underlying its beneficial effects. We showed that intraperitoneal administration of D3T significantly alleviated cognitive deficits in AD mice and dramatically decreased insoluble Aβ level and oxidative stress. Further mechanistic studies revealed that D3T significantly promoted hippocampal neurogenesis, and up-regulated levels of silent information regulator 1 (Sirt1), Nrf2 and heme oxygenase-1 (HO-1). Moreover, the positive effect of D3T on behavioral performance of AD mice was markedly attenuated by inhibition of the Sirt1/Nrf2 pathway by the antagonist EX527. In summary, our studies on a mouse AD model indicate that D3T could serve as a potential therapeutic agent for this devastating disease.

Original languageEnglish (US)
Pages (from-to)219-226
Number of pages8
JournalBehavioural Brain Research
Volume336
DOIs
StatePublished - Jan 15 2018

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Keywords

  • Alzheimer's disease
  • Cognition
  • D3T
  • Hippocampal neurogenesis
  • Nrf2
  • Oxidative stress
  • Sirt1

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Cui, Y. B., Ma, S. S., Zhang, C. Y., Li, D. P., Yang, B., Lv, P. J., Xing, Q., Huang, T., Yang, G. L., Cao, W., & Guan, F. X. (2018). Pharmacological activation of the Nrf2 pathway by 3H-1, 2-dithiole-3-thione is neuroprotective in a mouse model of Alzheimer disease. Behavioural Brain Research, 336, 219-226. https://doi.org/10.1016/j.bbr.2017.09.011