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siRNA Blocking of Mammalian Target of Rapamycin (mTOR) Attenuates Pathology in Annonacin-Induced Tauopathy in Mice

Neurotoxicity Research volume 35, pages 987–992 (2019)Cite this article

Abstract

Tauopathy is a pathological hallmark of many neurodegenerative diseases. It is characterized by abnormal aggregates of pathological phosphotau and somatodendritic redistribution. One suggested strategy for treating tauopathy is to stimulate autophagy, hence, getting rid of these pathological protein aggregates. One key controller of autophagy is mTOR. Since stimulation of mTOR leads to inhibition of autophagy, inhibitors of mTOR will cause stimulation of autophagy process. In this report, tauopathy was induced in mice using annonacin. Blocking of mTOR was achieved through stereotaxic injection of siRNA against mTOR. The behavioral and immunohistochemical evaluation revealed the development of tauopathy model as proven by deterioration of behavioral performance in open field test and significant tau aggregates in annonacin-treated mice. Blocking of mTOR revealed significant clearance of tau aggregates in the injected side; however, tau expression was not affected by mTOR blockage.

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Funding

The present work was supported by a grant from the Science and Technology Development Fund (STDF), Egypt (BARG: 13892; MS).

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Authors and Affiliations

  1. Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Elgomhourya street, Mansoura, 36551, Egypt

    Mohamed Salama, Sara El-Desouky, Aziza Alsayed, Mahmoud El-Hussiny & Khaled Magdy

  2. Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Mohamed Salama, Emad Fekry & Osama Shabka

  3. Internal Medicine Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt

    Sabry A. El-khodery & Mohamed A. Youssef

  4. Urology and Nephrology Center (UNC) Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Mohamed Sobh

  5. Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt

    Wael Mohamed

  6. Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic University, Kuantan, Pahang, Malaysia

    Wael Mohamed

Authors
  1. Mohamed Salama
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  2. Sara El-Desouky
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  3. Aziza Alsayed
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  4. Mahmoud El-Hussiny
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  5. Khaled Magdy
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  6. Emad Fekry
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  7. Osama Shabka
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  8. Sabry A. El-khodery
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  9. Mohamed A. Youssef
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  10. Mohamed Sobh
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  11. Wael Mohamed
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Correspondence to Mohamed Salama.

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Salama, M., El-Desouky, S., Alsayed, A. et al. siRNA Blocking of Mammalian Target of Rapamycin (mTOR) Attenuates Pathology in Annonacin-Induced Tauopathy in Mice. Neurotox Res 35, 987–992 (2019). https://doi.org/10.1007/s12640-018-9974-3

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  • DOI: https://doi.org/10.1007/s12640-018-9974-3

Keywords

  • Tauopathy
  • mTOR
  • siRNA
  • Neurodegeneration
  • Autophagy