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Neurotoxicity Research

, Volume 35, Issue 4, pp 987–992 | Cite as

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

  • Mohamed SalamaEmail author
  • Sara El-Desouky
  • Aziza Alsayed
  • Mahmoud El-Hussiny
  • Khaled Magdy
  • Emad Fekry
  • Osama Shabka
  • Sabry A. El-khodery
  • Mohamed A. Youssef
  • Mohamed Sobh
  • Wael Mohamed
SHORT COMMUNICATION

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.

Keywords

Tauopathy mTOR siRNA Neurodegeneration Autophagy 

Notes

Funding information

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mohamed Salama
    • 1
    • 2
    Email author
  • Sara El-Desouky
    • 1
  • Aziza Alsayed
    • 1
  • Mahmoud El-Hussiny
    • 1
  • Khaled Magdy
    • 1
  • Emad Fekry
    • 2
  • Osama Shabka
    • 2
  • Sabry A. El-khodery
    • 3
  • Mohamed A. Youssef
    • 3
  • Mohamed Sobh
    • 4
  • Wael Mohamed
    • 5
    • 6
  1. 1.Medical Experimental Research Center (MERC), Faculty of MedicineMansoura UniversityMansouraEgypt
  2. 2.Toxicology Department, Faculty of MedicineMansoura UniversityMansouraEgypt
  3. 3.Internal Medicine Department, Faculty of Veterinary MedicineMansoura UniversityMansouraEgypt
  4. 4.Urology and Nephrology Center (UNC) Faculty of MedicineMansoura UniversityMansouraEgypt
  5. 5.Department of Clinical Pharmacology, Faculty of MedicineMenoufia UniversityShebeen El-KomEgypt
  6. 6.Department of Basic Medical Science, Kulliyyah of MedicineInternational Islamic UniversityKuantanMalaysia

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