文献类型：期刊文献

英文题名：Sarsasapogenin-AA13 ameliorates Aβ-induced cognitive deficits via improving neuroglial capacity on Aβ clearance and antiinflammation

作者：Huang, Cui[1];Dong, Dong[1];Jiao, Qian[1];Pan, Hui[1];Ma, Lei[1];Wang, Rui[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai, Peoples R China

年份：2017

卷号：23

期号：6

起止页码：498

外文期刊名：CNS NEUROSCIENCE & THERAPEUTICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000403724900005)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 81072627, 81230090; Shanghai Biomedical Technology Support Program, Grant/Award Number: 15401901100; Key Project from Shanghai Science and Technology Committee, Grant/Award Number: 12431900901

语种：英文

外文关键词：antiinflammation; beta-amyloid clearance; neuroglia; phagocytosis; sarsasapogenin-AA13

摘要：Aims: Sarsasapogenin has been reported to improve dementia symptoms somehow, probably through modulating the function of cholinergic system, suppressing neurofibrillary tangles, and inhibiting inflammation. However, the role of sarsasapogenin in response to beta-amyloid (A beta) remains to be delineated. This study aimed to determine the therapeutic effect of sarsasapogenin-13 (AA13, a sarsasapogenin derivative) on learning and memory impairments in A beta-injected mice, as well as the role of AA13 in neuroglia-mediated antiinflammation and A beta clearance. Methods: Focusing on the role of AA13 in regulating glial responses to A beta, we conducted behavioral, morphological, and protein expression studies to explore the effects of AA13 on A beta clearance and inflammatory regulation. Results: The results indicated that oral administration of AA13 attenuated the memory deficits of intracerebroventricular (i.c.v.) A beta-injected mice; also, AA13 protected neuroglial cells against A beta-induced cytotoxicity. The further mechanical studies demonstrated that AA13 reversed the upregulation of proinflammatory M1 markers and increased the expression of antiinflammatory M2 markers in A beta-treated cells. Furthermore, AA13 facilitated A beta clearance through promoting A beta phagocytosis and degradation. AA13 modulated the expression of fatty acid translocase (CD36), insulin-degrading enzyme (IDE), neprilysin (NEP), and endothelin-converting enzyme (ECE) in neuroglia. Conclusion: The present study indicated that the neuroprotective effect of AA13 might relate to its modulatory effects on microglia activation state, phagocytic ability, and expression of A beta-degrading enzymes, which makes it a promising therapeutic agent in the early stage of Alzheimer's disease (AD).