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

Jung Hoon Koo, Eun Bum Kang, Yoo Sung Oh, Dae Seung Yang, Joon Yong Cho

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

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.

Original languageEnglish
Pages (from-to)142-152
Number of pages11
JournalExperimental Neurology
Volume288
DOIs
StatePublished - 1 Feb 2017

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Non-amyloidogenic pathway
  • Sirtuin-1
  • Treadmill exercise

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