PMID- 27812954
OWN - NLM
STAT- MEDLINE
DCOM- 20171024
LR  - 20211204
IS  - 1534-6307 (Electronic)
IS  - 1523-3774 (Print)
IS  - 1523-3774 (Linking)
VI  - 18
IP  - 12
DP  - 2016 Dec
TI  - Activation of the Mechanistic Target of Rapamycin in SLE: Explosion of Evidence 
      in the Last Five Years.
PG  - 73
LID - 10.1007/s11926-016-0622-8 [doi]
AB  - The mechanistic target of rapamycin (mTOR) is a central regulator in cell growth, 
      activation, proliferation, and survival. Activation of the mTOR pathway underlies 
      the pathogenesis of systemic lupus erythematosus (SLE). While mTOR activation and 
      its therapeutic reversal were originally discovered in T cells, recent 
      investigations have also uncovered roles in other cell subsets including B cells, 
      macrophages, and "non-immune" organs such as the liver and the kidney. Activation 
      of mTOR complex 1 (mTORC1) precedes the onset of SLE and associated 
      co-morbidities, such as anti-phospholipid syndrome (APS), and may act as an early 
      marker of disease pathogenesis. Six case reports have now been published that 
      document the development of SLE in patients with genetic activation of mTORC1. 
      Targeting mTORC1 over-activation with N-acetylcysteine, rapamycin, and rapalogs 
      provides an opportunity to supplant current therapies with severe side effect 
      profiles such as prednisone or cyclophosphamide. In the present review, we will 
      discuss the recent explosion of findings in support for a central role for mTOR 
      activation in SLE.
FAU - Oaks, Zachary
AU  - Oaks Z
AD  - Department of Medicine, College of Medicine, State University of New York Upstate 
      Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, State 
      University of New York Upstate Medical University, Syracuse, NY, 13210, USA.
FAU - Winans, Thomas
AU  - Winans T
AD  - Department of Medicine, College of Medicine, State University of New York Upstate 
      Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, State 
      University of New York Upstate Medical University, Syracuse, NY, 13210, USA.
FAU - Huang, Nick
AU  - Huang N
AD  - Department of Medicine, College of Medicine, State University of New York Upstate 
      Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA.
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, State 
      University of New York Upstate Medical University, Syracuse, NY, 13210, USA.
FAU - Banki, Katalin
AU  - Banki K
AD  - Department of Pathology, College of Medicine, State University of New York 
      Upstate Medical University, Syracuse, NY, 13210, USA.
FAU - Perl, Andras
AU  - Perl A
AD  - Department of Medicine, College of Medicine, State University of New York Upstate 
      Medical University, 750 East Adams Street, Syracuse, NY, 13210, USA. 
      perla@upstate.edu.
AD  - Department of Biochemistry and Molecular Biology, College of Medicine, State 
      University of New York Upstate Medical University, Syracuse, NY, 13210, USA. 
      perla@upstate.edu.
AD  - Department of Microbiology, and Immunology, College of Medicine, State University 
      of New York Upstate Medical University, Syracuse, NY, 13210, USA. 
      perla@upstate.edu.
LA  - eng
GR  - R01 DK078922/DK/NIDDK NIH HHS/United States
GR  - R34 AR068052/AR/NIAMS NIH HHS/United States
GR  - R01 AT004332/AT/NCCIH NIH HHS/United States
GR  - R01 AI122176/AI/NIAID NIH HHS/United States
GR  - R01 AI048079/AI/NIAID NIH HHS/United States
GR  - R01 AI072648/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Rheumatol Rep
JT  - Current rheumatology reports
JID - 100888970
RN  - 0 (Immunosuppressive Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/therapeutic use
MH  - B-Lymphocytes/*metabolism
MH  - Humans
MH  - Immunosuppressive Agents/therapeutic use
MH  - Lupus Erythematosus, Systemic/drug therapy/*metabolism
MH  - Sirolimus/therapeutic use
MH  - T-Lymphocytes/*metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5314949
MID - NIHMS847180
OTO - NOTNLM
OT  - Anti-phospholipid antibodies
OT  - B cells
OT  - Kidney
OT  - Liver
OT  - Macrophages
OT  - Mechanistic target of rapamycin
OT  - Mitochondria
OT  - Systemic lupus erythematosus
OT  - T cells
COIS- Conflict of Interest Drs. Oaks, Winans, Huang, Banki, and Perl declare no 
      conflicts of interest relevant to this manuscript.
EDAT- 2016/11/05 06:00
MHDA- 2017/10/25 06:00
PMCR- 2017/02/17
CRDT- 2016/11/05 06:00
PHST- 2016/11/05 06:00 [pubmed]
PHST- 2017/10/25 06:00 [medline]
PHST- 2016/11/05 06:00 [entrez]
PHST- 2017/02/17 00:00 [pmc-release]
AID - 10.1007/s11926-016-0622-8 [pii]
AID - 10.1007/s11926-016-0622-8 [doi]
PST - ppublish
SO  - Curr Rheumatol Rep. 2016 Dec;18(12):73. doi: 10.1007/s11926-016-0622-8.