Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Pharmacology & Pharmacy
Timothy Crook, Darshana Patil, Andrew Gaya, Nicholas Plowman, Sewanti Limaye, Anantbhushan Ranade, Amit Bhatt, Raymond Page, Dadasaheb Akolkar
Summary: The study demonstrated that patient-specific combination regimens with mTOR inhibition and other anti-neoplastic agents, selected based on multi-analyte molecular and functional profiling of the tumor, can result in meaningful outcomes in advanced or refractory solid organ cancers.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Pharmacology & Pharmacy
Ying-hua He, Guo Tian
Summary: Autophagy plays a crucial role in renal cell carcinoma, with many autophagy-related proteins serving as prognostic markers. Researchers are exploring synthetic and phytochemical drugs targeting autophagy for RCC therapy.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Wei Liu, Dong Zhao, Xiaofeng Wu, Fang Yue, Haizhen Yang, Ke Hu
Summary: Rapamycin can ameliorate obstructive sleep apnea-related renal injury by inhibiting the mTOR/NLRP3 signaling pathway, which is of great significance for the kidney health of patients with obstructive sleep apnea.
Article
Ophthalmology
Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Summary: Glaucoma, the second leading cause of blindness worldwide, is often treated with trabeculectomy, but this surgery can lead to excessive scarring and tissue fibrosis. Studies have shown that mTOR inhibitors may offer a new treatment modality for reducing fibrotic response in human conjunctival fibroblasts and improving bleb scarring after filtration surgery.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Surgery
Sunbin Ling, Qifan Zhan, Guangjiang Jiang, Qiaonan Shan, Lu Yin, Rui Wang, Qingyang Que, Xuyong Wei, Shengjun Xu, Jiongjie Yu, Wei Zhou, Lincheng Zhang, Jiaqi Bao, Qianwei Ye, Renyi Su, Rongli Wei, Jimin Liu, Kangchen Chen, Jingrui Wang, Haiyang Xie, Shusen Zheng, Xin He, Jiajia Xiang, Xiao Xu
Summary: This study discovered that E2F7 gene induces and promotes resistance to mTOR inhibitor sirolimus in HCC under hypoxic conditions. This is achieved by suppressing mTOR complex 1 and activating hypoxia-inducible factor-1 alpha and its downstream genes. Low expression of E2F7 can serve as an effective biomarker for predicting the response to anti-mTOR-based therapies after LT in HCC patients. Targeting E2F7 synergistically inhibits HCC growth with sirolimus.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Oncology
Fan Lin, Yunqi Liu, Lili Tang, Xiaohui Xu, Xueli Zhang, Yifan Song, Bicheng Chen, Yeping Ren, Xiangdong Yang
Summary: The study demonstrated that rapamycin protects against aristolochic acid-induced nephropathy by activating the mTOR-autophagy axis. This finding provides evidence for rapamycin as a promising pharmacological target for the treatment of aristolochic acid nephropathy.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Andrea Perez-Iturralde, Beatriz Carte, Rafael Aldabe
Summary: The study found that mTOR inhibitors have complex effects on AAV hepatic transduction efficiency, with rapamycin enhancing AAV transduction while RapaLink-1 and MLN0128 do not. This indicates that mTOR inhibition is not a straightforward strategy for improving AAV transduction, and more research is needed to elucidate the mechanisms involved in their effects.
HUMAN GENE THERAPY
(2021)
Review
Immunology
Jun Zeng, Qiang Zhong, Xiaobing Feng, Linde Li, Shijian Feng, Yu Fan, Turun Song, Zhongli Huang, Xianding Wang, Tao Lin
Summary: Conversion from CNIs to mTORi therapy in kidney transplant recipients can improve renal function and reduce the incidence of malignancy, but is associated with a higher risk of adverse events such as acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, leading to increased drug discontinuation rates. The conversion strategy may be suitable for selected patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Douglas R. Wassarman, Kondalarao Bankapalli, Leo J. Pallanck, Kevan M. Shokat
Summary: Mammalian target of rapamycin (mTOR) is a crucial factor in cell growth and metabolism, and its signaling in different tissues affects whole-organism processes. Researchers have developed selecTOR, a chemical-genetic system that restricts the activity of rapamycin analog in specific cell populations, achieving selective mTOR inhibition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Medicinal
Zhaoping Pan, Yi Chen, Haiying Pang, Xiaoyun Wang, Yuehua Zhang, Xin Xie, Gu He
Summary: A novel class of thieno [2,3-d] pyrimidine derivatives containing resorcinol and morpholine fragments as Hsp90/mTOR dual inhibitors were designed, synthesized, and evaluated. The most potent compound 17o showed remarkable inhibitory activities on Hsp90, mTOR, and SW780 cancer cell, both in vitro and in vivo. Mechanism studies revealed that 17o suppressed cell proliferation through the over-activation of the PI3K/AKT/mTOR pathway regulated by mTOR inhibition and apoptosis regulated by the mitochondrial pathway.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Md Mamunur Rashid, Hyunbeom Lee, Jinyoung Park, Byung Hwa Jung
Summary: This study evaluated metabolic differences after a single oral dose of first- and second-generation mTOR inhibitors using untargeted metabolomics and lipidomics approaches. It was found that a broad range of metabolites were affected by both generations of inhibitors, with more pronounced disparities within 8 hours after administration. Changes in fatty acids and glycerophospholipids patterns differed between the two generations of mTOR inhibitors, potentially due to the inhibition of mTORC2 subunit by the second-generation inhibitor. These findings could contribute to a more detailed understanding of key metabolic differences between first- and second-generation mTOR inhibitors.
BIOMEDICAL CHROMATOGRAPHY
(2021)
Article
Oncology
Jianya Huan, Petros Grivas, Jasmine Birch, Donna E. Hansel
Summary: The mammalian target of rapamycin (mTOR) pathway plays a crucial role in cell growth and metabolism. Dysregulation of this pathway can promote cancer growth and progression. Approximately 70% of bladder cancer (UC) cases show abnormal mTOR activity, indicating its key role in this cancer. This review highlights the importance of mTOR signaling in UC and its potential implications for future therapy. Despite extensive research on molecular alterations of the mTOR pathway in bladder cancer, there has been limited success in mTOR-targeted therapy. Further understanding of the signaling convergence onto mTOR complexes in bladder cancer may provide valuable insights for the treatment of this aggressive disease.
