Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model

Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophag...

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Main Authors:	Salama, Mohamed, Elhussiny, Mahmoud, Magdy, Alshimaa, Omran, Ahmed G., Alsayed, Aziza, Ashry, Ramy, Mohamed, Wael Mohamed Yousef
Format:	Article
Language:	English English English
Published:	Springer Nature 2018
Subjects:	QP Physiology R Medicine (General)
Online Access:	http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/30/58970_A%20Survey%20of%20schema%20matching%20research_complete.pdf http://irep.iium.edu.my/58970/13/58970_Dual%20mTORC1_scopus.pdf http://irep.iium.edu.my/58970/24/58970_Dual%20mTORC1-mTORC2%20blocker%20as%20a%20possible%20therapy_WoS.pdf

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spelling	iium-589702020-02-06T01:33:02Z http://irep.iium.edu.my/58970/ Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model Salama, Mohamed Elhussiny, Mahmoud Magdy, Alshimaa Omran, Ahmed G. Alsayed, Aziza Ashry, Ramy Mohamed, Wael Mohamed Yousef QP Physiology R Medicine (General) Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophagy to increase the ability to get rid of the unwanted tau aggregates. One of the key controllers of autophagy is mTOR. Blocking mTOR leads to stimulation of autophagy. Recently, unravelling molecular structure of mTOR showed that it is formed of two subunits: mTORC1/C2. So, blocking both subunits of mTOR seems more attractive as it will explore all abilities of mTOR molecule. In the present study, we report using pp242 which is a dual mTORC1/C2 blocker in cellular model of tauopathy using LUHMES cell line. Adding fenazaquin to LUHMES cells induced tauopathy in the form of increased phospho tau aggregates. Moreover, fenazaquin treated cells showed the characteristic somatic redistribution of tau. PP242 use in the present tauopathy model reversed the pathology significantly without observable cellular toxicity for the used dosage of 1000 nM. The present study suggests the possible use of pp242 as a dual mTOR blocker to treat tauopathy. Springer Nature 2018-04-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/58970/30/58970_A%20Survey%20of%20schema%20matching%20research_complete.pdf application/pdf en http://irep.iium.edu.my/58970/13/58970_Dual%20mTORC1_scopus.pdf application/pdf en http://irep.iium.edu.my/58970/24/58970_Dual%20mTORC1-mTORC2%20blocker%20as%20a%20possible%20therapy_WoS.pdf Salama, Mohamed and Elhussiny, Mahmoud and Magdy, Alshimaa and Omran, Ahmed G. and Alsayed, Aziza and Ashry, Ramy and Mohamed, Wael Mohamed Yousef (2018) Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model. Metabolic Brain Disorder, 33 (2). pp. 583-587. ISSN 0885-7490 E-ISSN 1573-7365 https://link.springer.com/article/10.1007%2Fs11011-017-0137-7 10.1007/s11011-017-0137-7
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English English English
topic	QP Physiology R Medicine (General)
spellingShingle	QP Physiology R Medicine (General) Salama, Mohamed Elhussiny, Mahmoud Magdy, Alshimaa Omran, Ahmed G. Alsayed, Aziza Ashry, Ramy Mohamed, Wael Mohamed Yousef Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
description	Tauopathy comprises a group of disorders caused by abnormal aggregates of tau protein. In these disorders phosphorylated tau protein tends to accumulate inside neuronal cells (soma) instead of the normal axonal distribution of tau. A suggested therapeutic strategy for tauopathy is to induce autophagy to increase the ability to get rid of the unwanted tau aggregates. One of the key controllers of autophagy is mTOR. Blocking mTOR leads to stimulation of autophagy. Recently, unravelling molecular structure of mTOR showed that it is formed of two subunits: mTORC1/C2. So, blocking both subunits of mTOR seems more attractive as it will explore all abilities of mTOR molecule. In the present study, we report using pp242 which is a dual mTORC1/C2 blocker in cellular model of tauopathy using LUHMES cell line. Adding fenazaquin to LUHMES cells induced tauopathy in the form of increased phospho tau aggregates. Moreover, fenazaquin treated cells showed the characteristic somatic redistribution of tau. PP242 use in the present tauopathy model reversed the pathology significantly without observable cellular toxicity for the used dosage of 1000 nM. The present study suggests the possible use of pp242 as a dual mTOR blocker to treat tauopathy.
format	Article
author	Salama, Mohamed Elhussiny, Mahmoud Magdy, Alshimaa Omran, Ahmed G. Alsayed, Aziza Ashry, Ramy Mohamed, Wael Mohamed Yousef
author_facet	Salama, Mohamed Elhussiny, Mahmoud Magdy, Alshimaa Omran, Ahmed G. Alsayed, Aziza Ashry, Ramy Mohamed, Wael Mohamed Yousef
author_sort	Salama, Mohamed
title	Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
title_short	Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
title_full	Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
title_fullStr	Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
title_full_unstemmed	Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model
title_sort	dual mtorc1/mtorc2 blocker as a possible therapy for tauopathy in cellular model
publisher	Springer Nature
publishDate	2018
url	http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/ http://irep.iium.edu.my/58970/30/58970_A%20Survey%20of%20schema%20matching%20research_complete.pdf http://irep.iium.edu.my/58970/13/58970_Dual%20mTORC1_scopus.pdf http://irep.iium.edu.my/58970/24/58970_Dual%20mTORC1-mTORC2%20blocker%20as%20a%20possible%20therapy_WoS.pdf
first_indexed	2023-09-18T21:23:27Z
last_indexed	2023-09-18T21:23:27Z
_version_	1777412035103948800

Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model

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