PMID- 27063582
OWN - NLM
STAT- MEDLINE
DCOM- 20170428
LR  - 20211204
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 280
DP  - 2016 Jun
TI  - RAD001 (everolimus) attenuates experimental autoimmune neuritis by inhibiting the 
      mTOR pathway, elevating Akt activity and polarizing M2 macrophages.
PG  - 106-14
LID - S0014-4886(16)30085-1 [pii]
LID - 10.1016/j.expneurol.2016.04.005 [doi]
AB  - Guillain-Barre' syndrome (GBS) is an acute, postinfectious, immune-mediated, 
      demyelinating disease of peripheral nerves and nerve roots. As a classical animal 
      model of GBS, experimental autoimmune neuritis (EAN) has become well-accepted. 
      Additionally, the potent immune modulation exerted by mammalian target of 
      rapamycin (mTOR) inhibitors has been used to treat cancers and showed beneficial 
      effects. Here we demonstrate that the mTOR inhibitor RAD001 (everolimus) 
      protected rats from the symptoms of EAN, as shown by decreased paralysis, 
      diminished inflammatory cell infiltration, reductions in demyelination of 
      peripheral nerves and improved nerve conduction. Furthermore, RAD001 shifted 
      macrophage polarization toward the protective M2 phenotype and modified the 
      inflammatory milieu by downregulating the production of pro-inflammatory 
      cytokines including IFN-gamma and IL-17as well as upregulating the release of 
      anti-inflammatory cytokines such as IL-4 and TGF-beta. Amounts of the mTOR 
      downstream targets p-P70S6K and p-4E-BP1 in sciatic nerves decreased, whereas the 
      level of its upstream protein p-Akt was elevated. This demonstrated that RAD001 
      inhibited the mTOR pathway and encouraged the expression of p-Akt, which led to 
      M2 macrophage polarization, thus improved the outcome of EAN in rats. 
      Consequently, RAD001 exhibits strong potential as a therapeutic strategy for 
      ameliorating peripheral poly-neuropathy.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Han, Ranran
AU  - Han R
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China.
FAU - Gao, Juan
AU  - Gao J
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China.
FAU - Zhai, Hui
AU  - Zhai H
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China.
FAU - Xiao, Jinting
AU  - Xiao J
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China.
FAU - Ding, Ya'nan
AU  - Ding Y
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China.
FAU - Hao, Junwei
AU  - Hao J
AD  - Department of Neurology, Tianjin Neurological Institute, Tianjin Medical 
      University General Hospital, Anshan Road, Heping District, Tianjin, 300052, 
      China. Electronic address: hjw@tmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20160408
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Polarity/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cytokines/genetics/metabolism
MH  - Disease Models, Animal
MH  - Electromyography
MH  - Everolimus/pharmacology/*therapeutic use
MH  - Freund's Adjuvant/toxicity
MH  - Immunosuppressive Agents/pharmacology/*therapeutic use
MH  - Lymphocytes/drug effects
MH  - Macrophages/drug effects
MH  - Male
MH  - Neural Conduction/drug effects
MH  - Neuritis, Autoimmune, Experimental/chemically induced/*drug therapy/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Experimental autoimmune neuritis
OT  - Guillain-Barre' syndrome
OT  - Macrophages
OT  - RAD001
OT  - mTOR
EDAT- 2016/04/12 06:00
MHDA- 2017/04/30 06:00
CRDT- 2016/04/12 06:00
PHST- 2016/01/21 00:00 [received]
PHST- 2016/03/28 00:00 [revised]
PHST- 2016/04/05 00:00 [accepted]
PHST- 2016/04/12 06:00 [entrez]
PHST- 2016/04/12 06:00 [pubmed]
PHST- 2017/04/30 06:00 [medline]
AID - S0014-4886(16)30085-1 [pii]
AID - 10.1016/j.expneurol.2016.04.005 [doi]
PST - ppublish
SO  - Exp Neurol. 2016 Jun;280:106-14. doi: 10.1016/j.expneurol.2016.04.005. Epub 2016 
      Apr 8.