| First Author | Zhang JY | Year | 2022 |
| Journal | Biochem Biophys Res Commun | Volume | 615 |
| Pages | 109-115 | PubMed ID | 35609415 |
| Mgi Jnum | J:340824 | Mgi Id | MGI:7295114 |
| Doi | 10.1016/j.bbrc.2022.05.053 | Citation | Zhang JY, et al. (2022) Activating transcription factor 6 regulates cystathionine to increase autophagy and restore memory in Alzheimer' s disease model mice. Biochem Biophys Res Commun 615:109-115 |
| abstractText | Endoplasmic reticulum stress (ER stress) plays a crucial role in the process of Alzheimer's disease (AD). Activating transcription factor 6 (ATF6) is a crucial sensor of ER stress. In AD patients, the homeostasis of the endogenous signal H2S produced by cystathionine gamma-lyase (CTH) is in disbalance. However, the role of ATF6 and CTH in AD is rarely reported. Herein, we found that ATF6 and CTH were reduced in AD patients and APP/PS1 mice by immunohistochemistry and western blots. In LN229 and U87 MG cells, knockdown of ATF6 attenuated CTH expression, whereas overexpression of ATF6 resulted in upregulation of CTH. Brain-specific ATF6 knockout mice expressed significantly down-regulated CTH in the hippocampus and cortex compared to wild-type mice. Mechanistically, ATF6 and CTH increased H2S generation and autophagy-related proteins. Further we observed that CTH promoted the sulfhydration of alphaSNAP. This is probably to be the specific mechanism by which AFT6 promotes autophagy. Through in vivo studies, we found that alphaSNAP sulfhydration expression was significantly lower in ATF6 knockout mice than in wild-type mice. Decreased ATF6 impaired spatial memory retention, while addition of CTH rescued memory loss. Together, we demonstrate that ATF6 positively regulates the expression of CTH, which is closely related to the rescue of AD. Targeting the ATF6/CTH signal pathway may provide a new strategy for the treatment of AD. |
