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

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

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Abstract

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.

Item Type:	Article (Journal)
Additional Information:	7497/58970
Uncontrolled Keywords:	Tau . mTOR . pp242 . Dual blocker
Subjects:	Q Science > QP Physiology R Medicine > R Medicine (General)
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Basic Medical
Depositing User:	Dr Wael Mohamed
Date Deposited:	03 Nov 2017 10:20
Last Modified:	06 Feb 2020 09:33
URI:	http://irep.iium.edu.my/id/eprint/58970

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