title: Treadmill exercise decreases amyloid-β burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease.
abstract: Accumulation of amyloid-β (Aβ) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aβ levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aβ 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 RARβ, ultimately facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation in SIRT-1 level also elevated PGC-1α level and reduced BACE-1 and C-99 level, resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus inhibit Aβ 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 Aβ production.
authors.affiliation: Department of Exercise Biochemistry, Korea National Sport University, Seoul 138-763, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Koo
authors.affiliation: Department of Exercise Biochemistry, Korea National Sport University, Seoul 138-763, Republic of Korea.
authors.forename: Eun-Bum
authors.initials: EB
authors.lastname: Kang
authors.affiliation: Department of Exercise Prescription, University of Seoul, Seoul 163, Republic of Korea.
authors.forename: Yoo-Sung
authors.initials: YS
authors.lastname: Oh
authors.affiliation: Department of Taekwondo Studies, University of Gachon, Gyeonggido, Republic of Korea. Electronic address: taekwon@gachon.ac.kr.
authors.forename: Dae-Seung
authors.initials: DS
authors.lastname: Yang
authors.affiliation: Department of Exercise Biochemistry, Korea National Sport University, Seoul 138-763, Republic of Korea. Electronic address: chojy86@knsu.ac.kr.
authors.forename: Joon-Yong
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000534:rehabilitation*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D010805:Physical Conditioning, Animal; D015398:Signal Transduction / Q000235:genetics*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D010751:Phosphopyruvate Hydratase
keywords: Alzheimer's disease; Amyloid-β; Non-amyloidogenic pathway; Sirtuin-1; Treadmill exercise