PMID- 30362086
OWN - NLM
STAT- MEDLINE
DCOM- 20190523
LR  - 20211204
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 35
IP  - 4
DP  - 2019 May
TI  - siRNA Blocking of Mammalian Target of Rapamycin (mTOR) Attenuates Pathology in 
      Annonacin-Induced Tauopathy in Mice.
PG  - 987-992
LID - 10.1007/s12640-018-9974-3 [doi]
AB  - 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.
FAU - Salama, Mohamed
AU  - Salama M
AUID- ORCID: 0000-0003-1644-0273
AD  - Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura 
      University, Elgomhourya street, Mansoura, 36551, Egypt. toxicsalama@hotmail.com.
AD  - Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt. 
      toxicsalama@hotmail.com.
FAU - El-Desouky, Sara
AU  - El-Desouky S
AD  - Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura 
      University, Elgomhourya street, Mansoura, 36551, Egypt.
FAU - Alsayed, Aziza
AU  - Alsayed A
AD  - Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura 
      University, Elgomhourya street, Mansoura, 36551, Egypt.
FAU - El-Hussiny, Mahmoud
AU  - El-Hussiny M
AD  - Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura 
      University, Elgomhourya street, Mansoura, 36551, Egypt.
FAU - Magdy, Khaled
AU  - Magdy K
AD  - Medical Experimental Research Center (MERC), Faculty of Medicine, Mansoura 
      University, Elgomhourya street, Mansoura, 36551, Egypt.
FAU - Fekry, Emad
AU  - Fekry E
AD  - Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
FAU - Shabka, Osama
AU  - Shabka O
AD  - Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
FAU - El-Khodery, Sabry A
AU  - El-Khodery SA
AD  - Internal Medicine Department, Faculty of Veterinary Medicine, Mansoura 
      University, Mansoura, Egypt.
FAU - Youssef, Mohamed A
AU  - Youssef MA
AD  - Internal Medicine Department, Faculty of Veterinary Medicine, Mansoura 
      University, Mansoura, Egypt.
FAU - Sobh, Mohamed
AU  - Sobh M
AD  - Urology and Nephrology Center (UNC) Faculty of Medicine, Mansoura University, 
      Mansoura, Egypt.
FAU - Mohamed, Wael
AU  - Mohamed W
AD  - Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, 
      Shebeen El-Kom, Egypt.
AD  - Department of Basic Medical Science, Kulliyyah of Medicine, International Islamic 
      University, Kuantan, Pahang, Malaysia.
LA  - eng
GR  - BARG 13892/Science and Technology Development Fund (STDF)/
PT  - Journal Article
DEP - 20181025
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Furans)
RN  - 0 (Lactones)
RN  - 0 (RNA, Small Interfering)
RN  - 40372ET6TM (annonacin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy
MH  - Brain/metabolism/*pathology
MH  - Furans
MH  - Lactones
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Neurons/metabolism/*pathology
MH  - Protein Aggregation, Pathological/metabolism
MH  - RNA, Small Interfering/administration & dosage
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
MH  - Tauopathies/chemically induced/metabolism/*pathology
OTO - NOTNLM
OT  - Autophagy
OT  - Neurodegeneration
OT  - Tauopathy
OT  - mTOR
OT  - siRNA
EDAT- 2018/10/27 06:00
MHDA- 2019/05/24 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/09/24 00:00 [received]
PHST- 2018/10/19 00:00 [accepted]
PHST- 2018/10/16 00:00 [revised]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2019/05/24 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - 10.1007/s12640-018-9974-3 [pii]
AID - 10.1007/s12640-018-9974-3 [doi]
PST - ppublish
SO  - Neurotox Res. 2019 May;35(4):987-992. doi: 10.1007/s12640-018-9974-3. Epub 2018 
      Oct 25.