| First Author | Na JY | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 484 |
| Issue | 4 | Pages | 890-895 |
| PubMed ID | 28188785 | Mgi Jnum | J:251358 |
| Mgi Id | MGI:6102203 | Doi | 10.1016/j.bbrc.2017.02.029 |
| Citation | Na JY, et al. (2017) Sortilin-related receptor 1 interacts with amyloid precursor protein and is activated by 6-shogaol, leading to inhibition of the amyloidogenic pathway. Biochem Biophys Res Commun 484(4):890-895 |
| abstractText | Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Abeta). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer''s disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22). We found that SORL1 siRNA treatment naturally inhibited SORL1 and led to increases in beta-secretase APP cleaving enzyme (BACE), secreted APP-beta (sAPPbeta) and Abeta. In contrast, 6-shogaol-mediated activation of SORL1 significantly downregulated BACE, sAPPbeta, and Abeta in both in vitro HT22 cells and in vivo APPSw/PS1-dE9 Tg mice. Therefore, SORL1 activation by 6-shogaol provides neuronal cell survival through the inhibition of Abeta production. These results indicate that 6-shogaol should be regarded as an SORL1 activator and a potential preventive agent for the treatment of AD. |
