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PPAR-α agonist regulates amyloid-β generation via inhibiting BACE-1 activity in human neuroblastoma SH-SY5Y cells transfected with APPswe gene

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Abstract

Alzheimer’s disease is a neuroinflammatory disease and is the most common cause of dementia in the elderly. Studies have shown the beneficial effects of the peroxisome proliferator-activated receptor alpha (PPAR-α) agonists on the treatment of neuroinflammatory diseases. The aim of the present study is to examine the ability of GW7647 (a PPAR-α agonist) to regulate amyloid precursor protein (APP) amyloidogenic processing in human neuroblastoma SH-SY5Y cells transfected with APPswe gene. After administration of GW7647 for 24 h, the levels of APP, soluble APPβ (sAPPβ), and presenilin 1 (PS-1) were assessed by Western blot. Cellular culture medium levels of amyloid-β 42 (Aβ42) were analyzed by ELISA, and the activity of beta-site APP cleaving enzyme 1 (BACE-1) was measured by fluorometric assay. We found that GW7647 decreased the expression of sAPPβ and the activity of BACE-1, and also reduced Aβ42 release. However, GW7647 did not modify the levels of APP and PS-1. Furthermore, LY294002, the phosphoinositide 3-kinase (PI3-K) inhibitor, reversed the effects of GW7647 on the BACE-1 activity and the levels of sAPPβ and Aβ42. Our data demonstrate that GW7647 may reduce Aβ production via inhibiting BACE-1 activity, and this may involve in PI3-K pathway.

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Abbreviations

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

BACE-1:

Beta-site amyloid precursor protein cleaving enzyme 1

PI3-K:

Phosphoinositide 3-kinase

PPAR-α:

Peroxisome proliferator-activated receptor alpha

PS1:

Presenilin 1

sAPPβ:

Soluble amyloid precursor protein beta

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Acknowledgments

This study was supported by the Science and Technology Research Project of Chongqing Municipal Education Commission (KJ1400227).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Chongqing, 400016, China

    Hua Zhang, Pei-feng Qiao, Feng-li Zhao & Yong Yan

  2. Special Wards, The Affiliated Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Ying Gao

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  1. Hua Zhang
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Correspondence to Hua Zhang or Yong Yan.

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Zhang, H., Gao, Y., Qiao, Pf. et al. PPAR-α agonist regulates amyloid-β generation via inhibiting BACE-1 activity in human neuroblastoma SH-SY5Y cells transfected with APPswe gene. Mol Cell Biochem 408, 37–46 (2015). https://doi.org/10.1007/s11010-015-2480-5

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