Activated protein C inhibits amyloid beta production via promoting expression of ADAM-10

作者：Li, Bing; Yu, Dawei; Xu, Zhiying^*

来源：Brain Research, 2014, 1545: 35-44.

DOI：10.1016/j.brainres.2013.12.005

• Alzheimer's disease
• Amyloid beta
• Activated protein C
• APP processing
• ADAM-10

Inhibition of A beta production and clearance of senile plaques have been considered as potential strategies in the treatment of Alzheimer's disease (AD). Activated protein C (APC) is an important factor in the anticoagulant system. However, whether APC can influence the condition of a chronic neurodegenerative process, such as that present in AD, is unknown. In this study, we found that administration of APC on AD Tg2576 mice significantly reduced amyloid beta production and helped to facilitate cognitive improvement. APC could also reduce levels of A beta 40 and A beta 42 produced in APPswe cells, an AD cell model. Further results demonstrated that APC did not change the levels of A beta-degrading enzymes, insulin-degrading enzyme (IDE), or neprilysin (NEP). Next, we found that APC promoted sAPP alpha and CTF alpha release and inhibited 5APP1 beta and CTF beta release, thereby indicating that APC could regulate A beta secretion by shifting APP processing from the amyloidogenic pathway toward the nonamyloidogenic pathway. Correspondingly, further study revealed that ADAM-10 expression was increased by APC, suggesting that APC inhibits A beta secretion through stimulating activity of alpha-secretase. These findings support the idea that APC could hold therapeutic potential in the treatment of AD.

• 出版日期2014-1-30
• 单位烟台毓璜顶医院; 青岛大学