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46713

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

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Last updated: 30 Jan 2023

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Abstract

Annonacin is a chemical compound with neurotoxic effects, it is a mitochondrial complex I inhibitor, causing taupathology. A neurodegenerative tauopathy is a pathological hallmark of many diseases as Parkinsonism. 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

DOI

10.21608/mjfmct.2019.46713

Keywords

Tauopathy, mTOR, siRNA, Neurodegeneration, autophagy

Authors

First Name

Mohamed

Last Name

Salama

MiddleName

-

Affiliation

Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Egypt/ Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Email

toxicsalama@hotmail.com

City

-

Orcid

-

First Name

Sara

Last Name

El-Desouky

MiddleName

-

Affiliation

Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Email

-

City

-

Orcid

-

First Name

Aziza

Last Name

Alsayed

MiddleName

-

Affiliation

Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Email

-

City

-

Orcid

-

First Name

Mahmoud

Last Name

El-Hussiny

MiddleName

-

Affiliation

Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Email

-

City

-

Orcid

-

First Name

Khaled

Last Name

Magdy

MiddleName

-

Affiliation

Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura University, Egypt.

Email

-

City

-

Orcid

-

First Name

Emad

Last Name

Fekry

MiddleName

-

Affiliation

Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Egypt.

Email

dremadfekry@yahoo.com

City

-

Orcid

-

First Name

Osama

Last Name

Shabka

MiddleName

A.

Affiliation

Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine, Mansoura University, Egypt.

Email

shabkaosama@gmail.com

City

-

Orcid

-

First Name

Sabry

Last Name

El-khodery

MiddleName

A

Affiliation

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

Email

-

City

-

Orcid

-

First Name

Mohamed

Last Name

Youssef

MiddleName

A

Affiliation

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

Email

-

City

-

Orcid

-

First Name

Mohamed

Last Name

Sobh

MiddleName

-

Affiliation

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

Email

-

City

-

Orcid

-

First Name

Wael

Last Name

Mohamed

MiddleName

-

Affiliation

Clinical Pharmacology Department, Faculty of Medicine, Menoufia University; Egypt

Email

-

City

-

Orcid

-

Volume

27

Article Issue

1

Related Issue

7043

Issue Date

2019-01-01

Receive Date

2019-09-01

Publish Date

2019-01-01

Page Start

67

Page End

75

Print ISSN

1110-5437

Online ISSN

2682-3217

Link

https://mjfmct.journals.ekb.eg/article_46713.html

Detail API

https://mjfmct.journals.ekb.eg/service?article_code=46713

Order

5

Type

Original Article

Type Code

966

Publication Type

Journal

Publication Title

Mansoura Journal of Forensic Medicine and Clinical Toxicology

Publication Link

https://mjfmct.journals.ekb.eg/

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Details

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Article

Created At

22 Jan 2023