MTOR a inhibitory mTOR

mTOR (mammalian target of rapamycin) is one of the important proteins of the signaling cascade. It is a serine/threonine kinase that is composed of 2549 amino acids, which corresponds to 289 kDa. In mammals, this protein occurs as mTORC1 (mTOR complex 1) and as mTORC2 (mTOR complex 2).

Function
mTOR, for example, is used in cell growth and cell survival, influences metabolic pathways (e.g. for insulin) and, last but not least, molecules used in signal propagation in the cell (growth factors, hormones). Functionally, it is part of the phosphatidylinositol 3-kinase (PI3K) family of enzymes due to its homologous C-terminus as that of PI3K. It is thus closely connected with the PI3K-AKT and the Ras-ERK pathways. It regulates translation initiation factor 4G (or eIF4G) as well as ribosomal 40S S6 kinase (S6K1/S6K2). Disorders of this protein are thought to be associated with diabetes mellitus and various types of cancer.

mTOR inhibitors
The best-known representative is rapamycin (sirolism), which was originally administered as an immunosuppressant used after transplants, but is now indicated especially for kidney cancers or metastatic breast tumors. Chemically, it is a low-molecular macrolide antibiotic produced by bacteria of the genus Streptomyces. Other representatives include everolimus and temsirolimus. The most common indication for the use of mTOR inhibitors is various types of cancer (that is, they serve as cytostatics), but the effect of these molecules on certain neurodegenerative diseases is also being intensively investigated.

Mechanism of action of mTOR inhibitors
By inhibiting mTOR, the synthesis of cyclin D is limited (the cell is stopped in the G1 phase cell cycle) and HIF-1a (as a result, VEGF is not expressed, which would induce neoangiogenesis).

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