title: mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging.
abstract: The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase, which plays pivotal roles in integrating growth signals on a cellular level. To support proliferation and survival under stress, two interacting complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation, and inhibit autophagy. Although rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Owing to oxidative stress, the activation of mTORC1 has emerged as a central pathway for the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. Paradoxically, mTORC1 has also been identified as a mediator of the Warburg effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR inhibitors are being developed to block not only transplant rejection and autoimmunity but also to treat obesity and various forms of cancer. Through preventing these diseases, personalized mTOR blockade holds promise to extend life span.
authors.affiliation: Division of Rheumatology, Department of Medicine State University of New York, Upstate Medical University, College of Medicine, Syracuse, New York.|Division of Rheumatology, Department of Microbiology and Immunology, State University of New York, Upstate Medical University, College of Medicine, Syracuse, New York.
authors.forename: Andras
authors.initials: A
authors.lastname: Perl
mesh_terms: D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D057285:Precision Medicine / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: T cell activation; autoimmunity; autophagy; biomarker; glutathione; glycolysis; hypoxia; inflammation; keloid disease; kynurenine; mTOR; metabolism; mitochondria; oxidative stress; pathogenesis; pentose phosphate pathway; rapamycin; sirolimus; systemic lupus erythematosus; treatment