No Significant Effect of 7,8-Dihydroxyflavone on APP Processing and Alzheimer-Associated Phenotypes

被引:17
|
作者
Zhou, Weitao [1 ,2 ]
Li, Xiaoyong [1 ,2 ]
Huang, Daochao [1 ,2 ]
Zhou, Weihui [1 ,2 ]
Li, Tingyu [1 ,2 ]
Song, Weihong [1 ,2 ,3 ]
机构
[1] Chongqing Med Univ, Childrens Hosp, Chongqing City Key Lab Translat Med Res Cognit De, Chongqing 400014, Peoples R China
[2] Chongqing Med Univ, Childrens Hosp, Key Lab Child Dev & Disorders, Minist Educ, Chongqing 400014, Peoples R China
[3] Univ British Columbia, Brain Res Ctr, Dept Psychiat, Townsend Family Labs, Vancouver, BC V6T 1Z3, Canada
基金
中国国家自然科学基金; 加拿大健康研究院;
关键词
A beta; Alzheimer's disease; 7,8-dihydroxyflavone; memory deficits; MEMORY DEFICITS; TRKB AGONIST; MOUSE MODEL; DISEASE; BDNF; SECRETASE; PATHOGENESIS; CLEAVAGE; PROTEIN; BACE2;
D O I
10.2174/1567205012666141218124243
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
It is reported that 7,8-dihydroxyflavone (DHF), a TrkB agonist, has beneficial effects on neuronal excitotoxicity, stroke, and Parkinson disease in animal models by enhancing axon regeneration, muscle reinnervation and neuromuscular transmission. The effect of DHF on AD neuropathology remains not well defined. In this study we examined whether DHF affects APP processing and cognitive functions in vitro and in vivo. We found that DHF had no significant effect on amyloid beta precursor protein (APP), BACE1 and amyloid beta protein (A beta). DHF had little effect on APP processing in cell cultures. DHF treatment did not reduce the deposition of A beta to form neuritic plaques in the brain of AD model mice APP23/PS45. Furthermore, DHF did not alleviate learning and memory impairments in the AD model mice. Our study suggest that further extensive and careful studies are warranted for considering DHF as a new therapeutic agent for reducing amyloid pathology and alleviating cognitive deficits for AD treatment.
引用
收藏
页码:47 / 52
页数:6
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