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mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging
Open accessAbstract
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.
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“The mTOR pathway has long been recognized to play a pivotal role in integrating signals at the cellular level and promote autoimmunity and carcinogenesis18,19.”
From Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation (2019) · cites this paper as [18]
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Mitochondrial dysfunction and oxidative stress in aging and cancer
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Metadata
- Authors
- Perl, A.
- Affiliations
- Division of Rheumatology, Department of Medicine State University of New York, Upstate Medical University College of Medicine Syracuse New York
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2015-04-23
- Volume
- 1346
- Issue
- 1
- Pages
- 33-44
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC4480196
- OpenAlex
- W1749413658
- Cited by
- 218
- References
- 144
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 9 · 2023: 16 · 2022: 18 · 2021: 26 · 2020: 20 · 2019: 29 · 2018: 31 · 2017: 20 · 2016: 21 · 2015: 5
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AI 048079, AI 072648)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mTOR, mTORC1, mTORC2, rapamycin, mTOR inhibitors, autoimmune disease, systemic lupus erythematosus, cancer, obesity, aging, Warburg effect, hypoxia, oxidative stress, autophagy, mRNA translation, biomarkers
- MeSH terms
- Aging, Animals, Autoimmune Diseases, Humans, Neoplasms, Obesity, Signal Transduction, Biomarkers, Sirolimus, Precision Medicine, TOR Serine-Threonine Kinases
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