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
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
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
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
Cell Biology
Mariana Borsa, Sandrine Obba, Felix C. Richter, Hanlin Zhang, Thomas Riffelmacher, Joana Carrelha, Ghada Alsaleh, Sten Eirik W. Jacobsen, Anna Katharina Simon
Summary: This study investigates the importance of autophagy in stem cells and finds that autophagy deficiency leads to stem cell loss and bone marrow failure, while inhibition of MTOR can rescue this loss and improve stem cell function.
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
Immunology
Preeti Vyas, Rajkumar Tulsawani, Divya Vohora
Summary: Recent findings show that neuroinflammation is closely related to seizures, and the PI3K/Akt/mTOR pathway is speculated to be a potential target for treating neuroinflammation-mediated seizures and neurodegeneration. In a study on mice, PI3K inhibitors buparlisib and dactolisib were found to be effective in prolonging seizure latency and reducing neuronal loss, while rapamycin showed some resistance. The study suggests that targeting the PI3K pathway may offer new approaches for seizure therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yipin Wang, Nicholas Siu Kay Fung, Wai-Ching Lam, Amy Cheuk Yin Lo
Summary: Recent advances in research have highlighted the importance of the mTOR signaling pathway in the treatment of ocular degenerative diseases. This pathway is regulated by oxidative stress, and understanding the complex relationship between mTOR and oxidative stress is crucial. Additionally, the role of mTOR-mediated autophagy in ocular degenerative diseases should not be overlooked.
Review
Pharmacology & Pharmacy
Xiang Li, Kuangqi Chen, Zixi Wang, Jiayuan Li, Xiawei Wang, Chen Xie, Jianping Tong, Ye Shen
Summary: Corneal diseases affect millions of people worldwide and current treatments have limitations. Activation of the mTOR signaling pathway is involved in the pathogenesis of various corneal diseases, and inhibition of mTOR with rapamycin has shown promising outcomes, indicating the potential of mTOR as a therapeutic target.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Calum Forteath, Ify Mordi, Raid Nisr, Erika J. Gutierrez-Lara, Noor Alqurashi, Iain R. Phair, Amy R. Cameron, Craig Beall, Ibrahim Bahr, Mohapradeep Mohan, Aaron K. F. Wong, Adel Dihoum, Anwar Mohammad, Colin N. A. Palmer, Douglas Lamont, Kei Sakamoto, Benoit Viollet, Marc Foretz, Chim C. Lang, Graham Rena
Summary: Using cellular approaches and proteomics, we found that metformin therapy for diabetes alters the regulation of branched chain amino acids through the suppression of the amino acid transporter SNAT2.
MOLECULAR METABOLISM
(2023)
Article
Neurosciences
Audrey J. Weber, Jeremy H. Herskowitz
Summary: ROCK2 is a kinase that regulates autophagy and cell skeleton contraction, playing a significant role in Alzheimer's disease by promoting the degradation of tau proteins, representing a potential therapeutic pathway for the disease.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
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)
Review
Biochemistry & Molecular Biology
Anastasia V. Poznyak, Vasily N. Sukhorukov, Alexander Zhuravlev, Nikolay A. Orekhov, Vladislav Kalmykov, Alexander N. Orekhov
Summary: Atherosclerosis has been a leading cause of death in developed countries for over a decade. The treatment and prevention of this disease are crucial, but there are still gaps in our understanding of its pathogenesis. The mTOR signaling pathway, although well-studied, continues to reveal new details. Therapeutic strategies associated with rapamycin have shown promise in other diseases, suggesting potential effectiveness in atherosclerosis as well.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Marina Garcia-Macia, Adrian Santos-Ledo, Jack Leslie, Hannah L. Paish, Amy L. Collins, Rebecca S. Scott, Abigail Watson, Rachel A. Burgoyne, Steve White, Jeremy French, John Hammond, Lee A. Borthwick, Jelena Mann, Juan P. Bolanos, Viktor Korolchuk, Fiona Oakley, Derek A. Mann
Summary: This study investigated the molecular mechanisms of liver lipophagy in NAFLD. It was found that mTORC1 phosphorylates Plin3 to promote LD degradation, suggesting a potential therapeutic strategy for enhancing lipophagy in hepatocytes to protect against lipid-mediated toxicity in NAFLD.
