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mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer
The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complex...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603867/ https://www.ncbi.nlm.nih.gov/pubmed/36293326 http://dx.doi.org/10.3390/ijms232012470 |
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author | Afzal, Obaid Altamimi, Abdulmalik S. A. Mubeen, Bismillah Alzarea, Sami I. Almalki, Waleed Hassan Al-Qahtani, Salwa D. Atiya, Eman M. Al-Abbasi, Fahad A. Ali, Fatima Ullah, Inam Nadeem, Muhammad Shahid Kazmi, Imran |
author_facet | Afzal, Obaid Altamimi, Abdulmalik S. A. Mubeen, Bismillah Alzarea, Sami I. Almalki, Waleed Hassan Al-Qahtani, Salwa D. Atiya, Eman M. Al-Abbasi, Fahad A. Ali, Fatima Ullah, Inam Nadeem, Muhammad Shahid Kazmi, Imran |
author_sort | Afzal, Obaid |
collection | PubMed |
description | The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer. |
format | Online Article Text |
id | pubmed-9603867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96038672022-10-27 mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer Afzal, Obaid Altamimi, Abdulmalik S. A. Mubeen, Bismillah Alzarea, Sami I. Almalki, Waleed Hassan Al-Qahtani, Salwa D. Atiya, Eman M. Al-Abbasi, Fahad A. Ali, Fatima Ullah, Inam Nadeem, Muhammad Shahid Kazmi, Imran Int J Mol Sci Review The mammalian target of rapamycin (mTOR) is the major controller of a number of important cellular activities, including protein synthesis, cell expansion, multiplication, autophagy, lysosomal function, and cellular metabolism. When mTOR interacts with specific adaptor proteins, it forms two complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The mTOR signaling system regulates gene transcription and protein manufacturing to control proliferation of cell, differentiation of immune cell, and tumor metabolism. Due to its vital role in case of microbial infections, inflammations and cancer development and progression, mTOR has been considered as a key therapeutic target for the development of targeted medication. As autophagy dysfunction is linked to changes in both innate and adaptive immune responses, bacterial clearance defects, and goblet and Paneth cell malfunction, all of these changes are linked to inflammatory bowel diseases (IBD) and colorectal cancer (CRC) pathogenesis. Preclinical and clinical data have shown that the inhibition and induction of autophagy have significant potential to be translated into the clinical applications. In IBD and several CRC models, mTORC1 inhibitors have been found effective. In the recent years, a number of novel mTOR inhibitors have been investigated in clinical trials, and a number of drugs have shown considerably enhanced efficacy when combined with mTOR inhibitors. The future developments in the mTOR targeting medications can benefit patients in individualized therapy. Advanced and innovative medicines that are more effective and have lower drug resistance are still in high demand. New findings could be relevant in medicine development, pharmacological modification, or future mTOR inhibitor research. Therefore, the goal of this review is to present a comprehensive account of current developments on the mTOR pathway and its inhibitors, with an emphasis on the management of microbial infections, the treatment of inflammatory bowel disease, and the management of colon cancer. MDPI 2022-10-18 /pmc/articles/PMC9603867/ /pubmed/36293326 http://dx.doi.org/10.3390/ijms232012470 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Afzal, Obaid Altamimi, Abdulmalik S. A. Mubeen, Bismillah Alzarea, Sami I. Almalki, Waleed Hassan Al-Qahtani, Salwa D. Atiya, Eman M. Al-Abbasi, Fahad A. Ali, Fatima Ullah, Inam Nadeem, Muhammad Shahid Kazmi, Imran mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title | mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title_full | mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title_fullStr | mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title_full_unstemmed | mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title_short | mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer |
title_sort | mtor as a potential target for the treatment of microbial infections, inflammatory bowel diseases, and colorectal cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9603867/ https://www.ncbi.nlm.nih.gov/pubmed/36293326 http://dx.doi.org/10.3390/ijms232012470 |
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