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...
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12470 |
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| author | Obaid Afzal Abdulmalik S. A. Altamimi Bismillah Mubeen Sami I. Alzarea Waleed Hassan Almalki Salwa D. Al-Qahtani Eman M. Atiya Fahad A. Al-Abbasi Fatima Ali Inam Ullah Muhammad Shahid Nadeem Imran Kazmi |
| author_facet | Obaid Afzal Abdulmalik S. A. Altamimi Bismillah Mubeen Sami I. Alzarea Waleed Hassan Almalki Salwa D. Al-Qahtani Eman M. Atiya Fahad A. Al-Abbasi Fatima Ali Inam Ullah Muhammad Shahid Nadeem Imran Kazmi |
| author_sort | Obaid Afzal |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T20:06:06Z |
| format | Article |
| id | doaj.art-b188db13341441b5a82a5bec5d1e3330 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:06:06Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b188db13341441b5a82a5bec5d1e33302023-11-24T00:32:07ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201247010.3390/ijms232012470mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal CancerObaid Afzal0Abdulmalik S. A. Altamimi1Bismillah Mubeen2Sami I. Alzarea3Waleed Hassan Almalki4Salwa D. Al-Qahtani5Eman M. Atiya6Fahad A. Al-Abbasi7Fatima Ali8Inam Ullah9Muhammad Shahid Nadeem10Imran Kazmi11Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaInstitute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54590, PakistanDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Science, Majmaah University, Al-Majmaah 11952, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaInstitute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54590, PakistanInstitute of Molecular Biology and Biotechnology, The University of Lahore, Lahore 54590, PakistanDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi ArabiaThe 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.https://www.mdpi.com/1422-0067/23/20/12470mammalian target of rapamycin (mTOR)inflammatory bowel diseases (IBD)colorectal cancer (CRC) |
| spellingShingle | Obaid Afzal Abdulmalik S. A. Altamimi Bismillah Mubeen Sami I. Alzarea Waleed Hassan Almalki Salwa D. Al-Qahtani Eman M. Atiya Fahad A. Al-Abbasi Fatima Ali Inam Ullah Muhammad Shahid Nadeem Imran Kazmi mTOR as a Potential Target for the Treatment of Microbial Infections, Inflammatory Bowel Diseases, and Colorectal Cancer International Journal of Molecular Sciences mammalian target of rapamycin (mTOR) inflammatory bowel diseases (IBD) colorectal cancer (CRC) |
| 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 | mammalian target of rapamycin (mTOR) inflammatory bowel diseases (IBD) colorectal cancer (CRC) |
| url | https://www.mdpi.com/1422-0067/23/20/12470 |
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