siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice

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...

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Main Authors: Salama, Mohamed M., El-Desouky, Sara, Alsayed, Aziza, El-Hussiny, Mahmoud, Magdy, Khaled, Fekry, Emad, Shabka, Osama, El-Khodery, Sabry A., Youssef, Mohamed A., Sobh, Mohamed, Mohamed, Wael Mohamed Yousef
Format: Article
Language:English
English
English
Published: Springer Nature Switzerland AG 2019
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Online Access:http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/1/mTOR.pdf
http://irep.iium.edu.my/67119/7/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20%28mTOR%29%20Attenuates%20Pathology%20in%20Annonacin-Induced%20Tauopathy%20in%20Mice_wos.pdf
http://irep.iium.edu.my/67119/13/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20mTOR_scopus.pdf
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recordtype eprints
spelling iium-671192019-08-05T06:12:34Z http://irep.iium.edu.my/67119/ siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice Salama, Mohamed M. El-Desouky, Sara Alsayed, Aziza El-Hussiny, Mahmoud Magdy, Khaled Fekry, Emad Shabka, Osama El-Khodery, Sabry A. Youssef, Mohamed A. Sobh, Mohamed Mohamed, Wael Mohamed Yousef R Medicine (General) RM300 Drugs and their action 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. Springer Nature Switzerland AG 2019-05 Article PeerReviewed application/pdf en http://irep.iium.edu.my/67119/1/mTOR.pdf application/pdf en http://irep.iium.edu.my/67119/7/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20%28mTOR%29%20Attenuates%20Pathology%20in%20Annonacin-Induced%20Tauopathy%20in%20Mice_wos.pdf application/pdf en http://irep.iium.edu.my/67119/13/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20mTOR_scopus.pdf Salama, Mohamed M. and El-Desouky, Sara and Alsayed, Aziza and El-Hussiny, Mahmoud and Magdy, Khaled and Fekry, Emad and Shabka, Osama and El-Khodery, Sabry A. and Youssef, Mohamed A. and Sobh, Mohamed and Mohamed, Wael Mohamed Yousef (2019) siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice. Neurotoxicity Research, 35 (4). pp. 987-992. ISSN 1029-8428 E-ISSN 1476-3524 (In Press) https://link.springer.com/article/10.1007/s12640-018-9974-3 10.1007/s12640-018-9974-3
repository_type Digital Repository
institution_category Local University
institution International Islamic University Malaysia
building IIUM Repository
collection Online Access
language English
English
English
topic R Medicine (General)
RM300 Drugs and their action
spellingShingle R Medicine (General)
RM300 Drugs and their action
Salama, Mohamed M.
El-Desouky, Sara
Alsayed, Aziza
El-Hussiny, Mahmoud
Magdy, Khaled
Fekry, Emad
Shabka, Osama
El-Khodery, Sabry A.
Youssef, Mohamed A.
Sobh, Mohamed
Mohamed, Wael Mohamed Yousef
siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
description 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.
format Article
author Salama, Mohamed M.
El-Desouky, Sara
Alsayed, Aziza
El-Hussiny, Mahmoud
Magdy, Khaled
Fekry, Emad
Shabka, Osama
El-Khodery, Sabry A.
Youssef, Mohamed A.
Sobh, Mohamed
Mohamed, Wael Mohamed Yousef
author_facet Salama, Mohamed M.
El-Desouky, Sara
Alsayed, Aziza
El-Hussiny, Mahmoud
Magdy, Khaled
Fekry, Emad
Shabka, Osama
El-Khodery, Sabry A.
Youssef, Mohamed A.
Sobh, Mohamed
Mohamed, Wael Mohamed Yousef
author_sort Salama, Mohamed M.
title siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
title_short siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
title_full siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
title_fullStr siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
title_full_unstemmed siRNA blocking of mammalian target of rapamycin (mTOR) attenuates pathology in annonacin-induced tauopathy in mice
title_sort sirna blocking of mammalian target of rapamycin (mtor) attenuates pathology in annonacin-induced tauopathy in mice
publisher Springer Nature Switzerland AG
publishDate 2019
url http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/
http://irep.iium.edu.my/67119/1/mTOR.pdf
http://irep.iium.edu.my/67119/7/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20%28mTOR%29%20Attenuates%20Pathology%20in%20Annonacin-Induced%20Tauopathy%20in%20Mice_wos.pdf
http://irep.iium.edu.my/67119/13/67119_siRNA%20Blocking%20of%20Mammalian%20Target%20of%20Rapamycin%20mTOR_scopus.pdf
first_indexed 2023-09-18T21:35:18Z
last_indexed 2023-09-18T21:35:18Z
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