Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease

被引:119
作者
Koo, Jung-Hoon [1 ]
Kang, Eun-Bum [1 ]
Oh, Yoo-Sung [2 ]
Yang, Dae-Seung [3 ]
Cho, Joon-Yong [1 ]
机构
[1] Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea
[2] Univ Seoul, Dept Exercise Prescript, Seoul 163, South Korea
[3] Univ Gachon, Dept Taekwondo Studies, Gyeonggido, South Korea
关键词
Alzheimer's disease; Amyloid-beta; Treadmill exercise; Sirtuin-1; Non-amyloidogenic pathway; PRECURSOR PROTEIN; CALORIE RESTRICTION; VOLUNTARY EXERCISE; ALPHA-SECRETASE; TRANSGENIC MICE; A-BETA; PATHOGENIC PHENOTYPES; FORCED EXERCISE; GENE-EXPRESSION; UP-REGULATION;
D O I
10.1016/j.expneurol.2016.11.014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Accumulation of amyloid-beta (A beta) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces A beta levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases All production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RAR beta, ultimately facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation in SIRT-1 level also elevated PGC-1 alpha level and reduced BACE-1 and C-99 level, resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus inhibit Ala production via upregulation of SIRT-1, which biases amyloid precursor protein processing toward the non-amyloidogenic pathway. This study provides novel and valuable insight into the molecular mechanisms possibly by which treadmill exercise reduces A beta production. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:142 / 152
页数:11
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