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Brain Microvascular Endothelial Cell Derived Exosomes Potently Ameliorate Cognitive Dysfunction by Enhancing the Clearance of Aβ Through Up-Regulation of P-gp in Mouse Model of AD

Neurochemical Research volume 45, pages 2161–2172 (2020)Cite this article

Abstract

Accumulation of amyloid-β (Aβ) peptides in the brain is regarded as a major contributor to the pathogenesis and progression of Alzheimer's disease (AD). P-glycoprotein (P-gp) as a member of ABC transporter family situated in blood brain barrier (BBB) plays a role on cleaning of Aβ via its efflux transport effect in the treatment of AD. However, the expression of P-gp in pathological BBB was lower than that in normal BBB, thus impeding the clearance of Aβ. Here, we used human brain microvascular endothelial cells (HBMVECs) derived exosomes (HBMVECs-Ex) inheriting P-gp as an extracorporeal Aβ cleansing system to remove Aβ peptides from the brain by specific capture between P-gp and Aβ. The results showed that HBMVECs-Ex inheriting P-gp greatly facilitated the cerebral clearance of Aβ by effectively transporting Aβ out of brain and potently ameliorated cognitive dysfunction in AD mice. Taken together, HBMVECs-Ex provided a new strategy on the treatment of AD.

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Acknowledgements

This work was supported by Scientific Research Project of Liaoning Provincial Department of Education (JYTQN201719) and Natural Science Foundation of Liaoning Province (2019-ZD-0808). We thank the support of the above funds.

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Affiliations

  1. School of Pharmacy, Jinzhou Medical University, Jinzhou, 121000, People’s Republic of China

    Junlu Pan, Ruyi He, Qinghao Huo, Yijie Shi & Liang Zhao

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  1. Junlu Pan
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  2. Ruyi He
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  3. Qinghao Huo
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  4. Yijie Shi
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  5. Liang Zhao
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Contributions

JP performed all experiments and wrote the manuscript; RH and QH helped with the animal experiments and biological study; YS and LZ conducted and supervised the whole experiments. All authors read and approved the final manuscript.

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Correspondence to Yijie Shi or Liang Zhao.

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Pan, J., He, R., Huo, Q. et al. Brain Microvascular Endothelial Cell Derived Exosomes Potently Ameliorate Cognitive Dysfunction by Enhancing the Clearance of Aβ Through Up-Regulation of P-gp in Mouse Model of AD. Neurochem Res 45, 2161–2172 (2020). https://doi.org/10.1007/s11064-020-03076-1

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  • DOI: https://doi.org/10.1007/s11064-020-03076-1

Keywords

  • Amyloid-β
  • Alzheimer’s disease
  • P-glycoprotein
  • Blood–brain barrier
  • HBMVECs-Ex