共 55 条
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
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机构:
Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea

Kang, Eun-Bum
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机构:
Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea

Oh, Yoo-Sung
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机构:
Univ Seoul, Dept Exercise Prescript, Seoul 163, South Korea Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea

Yang, Dae-Seung
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h-index: 0
机构:
Univ Gachon, Dept Taekwondo Studies, Gyeonggido, South Korea Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea

Cho, Joon-Yong
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h-index: 0
机构:
Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea Korea Natl Sport Univ, Dept Exercise Biochem, Seoul 138763, South Korea
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.
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页码:142 / 152
页数:11
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Hosp Duran & Reynals, Bellvitge Biomed Res Inst IDIBELL, Inst Neuropathol, Neurometabol Dis Lab, Barcelona, Spain
ISCIII, Ctr Biomed Res Rare Dis CIBERER, U579, Valencia, Spain
Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA

Beal, M. Flint
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机构:
Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA Weill Cornell Med Coll, Dept Neurol & Neurosci, New York, NY 10065 USA