Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian target of rapamycin (mTOR) inhibitors (mTORis) constitute a relatively new category of immunosuppressive and antineoplastic drugs. These share a unique mechanism of action that is focused on the inhibition of the mTOR. Their clinical applications have recently expanded significantly to cover a wide spectrum of immune and non-immune-mediated disorders, including, apart from solid organ transplantation, various solid organ and haematological malignancies, rheumatological and auto-immune diseases such as rheumatoid arthritis, systemic lupus erythematosus, fibrotic conditions, e.g. pulmonary and hepatic fibrosis, and even metabolic problems such as diabetes mellitus and obesity. The most challenging and frequent adverse effects of the mTORis are the haematological ones, especially anaemia, leukopenia and thrombocytopenia. A unique characteristic of mTORi-induced anaemia is concurrent marked microcytosis. Recently, mechanisms have been proposed to explain the microcytic appearance of this anaemia; these include globin production defect, erythropoietin resistance, chronic inflammation, dysregulation of cellular iron metabolism and hepcidin-mediated iron homeostasis interference. As the differential diagnosis of microcytic anaemia includes pure iron deficiency, functional iron deficiency and haemoglobinopathies, characterization of the anaemia requires significant investigation, time and costs. Therefore, understanding of the likely interaction between mTORis and patients is valuable in clinical practice. Moreover, this could expand the drugs' therapeutic applications to other disorders, and suggest novel targets for further research.
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PMID:Mammalian target of rapamycin (mTOR) inhibitors: potential uses and a review of haematological adverse effects. 2124 19

Red blood cells (RBC) must coordinate their rate of growth and proliferation with the availability of nutrients, such as iron, but the signaling mechanisms that link the nutritional state to RBC growth are incompletely understood. We performed a screen for cell types that have high levels of signaling through mTORC1, a protein kinase that couples nutrient availability to cell growth. This screen revealed that reticulocytes show high levels of phosphorylated ribosomal protein S6, a downstream target of mTORC1. We found that mTORC1 activity in RBCs is regulated by dietary iron and that genetic activation or inhibition of mTORC1 results in macrocytic or microcytic anemia, respectively. Finally, ATP competitive mTOR inhibitors reduced RBC proliferation and were lethal after treatment with phenylhydrazine, an inducer of hemolysis. These results identify the mTORC1 pathway as a critical regulator of RBC growth and proliferation and establish that perturbations in this pathway result in anemia.
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PMID:A critical role for mTORC1 in erythropoiesis and anemia. 2520 74