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Treadmill Exercise Attenuates α-Synuclein Levels by Promoting Mitochondrial Function and Autophagy Possibly via SIRT1 in the Chronic MPTP/P-Induced Mouse Model of Parkinson’s Disease

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An Erratum to this article was published on 24 July 2017

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Abstract

Accumulation of alpha-synuclein (α-Syn) is significantly correlated with the presence of progressive motor deficits, which is the main symptom of Parkinson’s disease (PD). Although physical exercise reduces α-Syn levels, the molecular mechanisms by which physical exercise decreases α-Syn remain unclear. We hypothesized that treadmill exercise (TE) decreases α-Syn levels by improving mitochondrial function and promoting autophagy via the sirtuin-1 (SIRT1) signaling pathway in the chronic 1-methyl-1,2,3,6-tetrahydropyridine with probenecid (MPTP/P)-induced mouse model of PD. We found that TE reduces α-Syn levels, which subsequently ameliorates dopaminergic (DAergic) neuron loss and α-Syn-mediated apoptotic cell death. Most importantly, TE increases SIRT1 expression, which results in increased mitochondrial biogenesis and decreased oxidative stress by activating peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). SIRT1 activation by TE also promotes autophagic clearance of α-Syn by inducing the activation of microtubule-associated protein 1 light chain 3 (LC3). Collectively, our results demonstrate that TE may reduce α-Syn levels by improving mitochondrial function and increasing autophagic flux, thereby ameliorating chronic MPTP/P-induced motor deficits in PD mice.

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  • 24 July 2017

    An erratum to this article has been published.

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Authors and Affiliations

  1. Department of Exercise Biochemistry, Korea National Sport University, Seoul, 138-763, Republic of Korea

    Jung-Hoon Koo & Joon-Yong Cho

  2. Institute of Sport Science, Korea National Sport University, Seoul, 138-763, Republic of Korea

    Jung-Hoon Koo

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  1. Jung-Hoon Koo
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Correspondence to Joon-Yong Cho.

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All experiments were approved by the Institutional Animal Care and Use Committee at Korea National Sport University and by the Korea Food and Drug Administration (FDA). All mice were carried out in an accredited Korea FDA animal facility in accordance with the AAALAC International Animal Care Policies.

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The authors declare that they have no conflicts of interest.

Additional information

The original version of this article was revised: An error occurred in Fig. 8A during the final stages of figure mounting. The published bottom panel of Fig. 8A was inappropriately mounted with the wrong GAPDH Western blot control.

An erratum to this article is available at https://doi.org/10.1007/s12640-017-9779-9.

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Koo, JH., Cho, JY. Treadmill Exercise Attenuates α-Synuclein Levels by Promoting Mitochondrial Function and Autophagy Possibly via SIRT1 in the Chronic MPTP/P-Induced Mouse Model of Parkinson’s Disease. Neurotox Res 32, 473–486 (2017). https://doi.org/10.1007/s12640-017-9770-5

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