6-Shogaol has anti-amyloidogenic activity and ameliorates Alzheimer’s disease via CysLT1R-mediated inhibition of cathepsin B

• Published in: Biochemical and biophysical research communications Vol. 477; no. 1; pp. 96 - 102
• Main Authors: Na, Ji-Young, Song, Kibbeum, Lee, Ju-Woon, Kim, Sokho, Kwon, Jungkee
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.08.2016
• Subjects: 6-Shogaol; Alzheimer Disease - prevention & control; Alzheimer’s disease; Amyloid beta-Peptides - antagonists & inhibitors; Animals; Avoidance Learning - drug effects; Brain - drug effects; Brain - enzymology; Brain - metabolism; Catechols - pharmacology; Cathepsin B; Cathepsin B - antagonists & inhibitors; Cell Line; Cysteinyl leukotriene 1 receptor; Ginger; Male; Maze Learning - drug effects; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments - antagonists & inhibitors; Receptors, Leukotriene - physiology; Aβ; APP; CysLT1R; MWM; AD; 5-LO; 6-Shogaol; Alzheimer’s disease; APP/PS1; Cathepsin B; Ginger; Cysteinyl leukotriene 1 receptor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.06.026

Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, the effects of 6-shogaol on Alzheimer’s disease (AD) have not yet been investigated. Here we aimed to determine whether 6-shogaol exerts neuroprotective effects against AD. Specifically, we investigated the effects of 6-shogaol on the cysteinyl leukotriene 1 receptor (CysLT1R), a major factor in AD pathogenesis. Moreover, we clarified the relationship between CysLT1R and cathepsin B, a cysteine protease. We used in vitro and in vivo models to determine whether 6-shogaol inhibits CysLT1R/cathepsin B in an amyloid-beta (Aβ; 1–42)-induced model of neurotoxicity. We first confirmed that CysLT1R and cathepsin B are upregulated by Aβ (1-42) and that CysLT1R activation induces cathepsin B. In contrast, we found that 6-shogaol-mediated inhibition of CysLT1R downregulates cathepsin B in both in vitro and in vivo models. Furthermore, we found that 6-shogaol-mediated inhibition of CysLT1R/cathepsin B reduces Aβ deposition in the brain and ameliorates behavioral deficits in APPSw/PS1-dE9 Tg mice. Our results indicate that 6-shogaol is a CysLT1R/cathepsin B inhibitor and is a novel potential therapeutic agent for the treatment of various neurodegenerative diseases, including AD. [Display omitted] •6-shogaol reduces Aβ (1–42)-induced cytotoxicity.•6-shogaol ameliorates CysLT1R/cathepsin B expression.•6-shogaol improves learning and memory impairment.