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
Neurosciences
Meng- Zhao, Houting Lv, Na Yang, Guang-Hua Peng
Summary: The study investigated the mechanism of retinal photoreceptor degeneration by establishing a stable retinitis pigmentosa (RP) model. It was found that activation of mTOR may be associated with RP, and the use of mTOR inhibitor rapamycin improved retinal function and photoreceptor thickness and morphology, possibly by activating autophagy to protect retinal photoreceptors.
FRONTIERS IN NEUROSCIENCE
(2022)
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
Pharmacology & Pharmacy
Martina P. Morawe, Fan Liao, Willi Amberg, Jeroen van Bergeijk, Rui Chang, Mary Gulino, Caitlin Hamilton, Carolin Hoft, Casey Lumpkin, Bryan Mastis, Emily McGlame, Judith Nuber, Christian Plaas, Brinda Ravikumar, Kaushambi Roy, Marion Schanzenbaecher, Joseph Tierno, Viktor Lakics, Tammy Dellovade, Matthew Townsend
Summary: In this study, the researchers aimed to reduce tau pathology in Alzheimer's Disease by activating mTOR-dependent autophagy. They found that mTOR inhibitors could effectively reduce tau pathology, with PQR530 showing better results even when treatment was started after the onset of pathology. The researchers concluded that intermittent dosing of mTOR inhibitors can have a disease-modifying effect in AD.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Qian Wu, Qianyu Lv, Xiao'an Liu, Xuejiao Ye, Linlin Cao, Manshi Wang, Junjia Li, Yingtian Yang, Lanlan Li, Shihan Wang
Summary: Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases. The activation of the mechanistic/mammalian target of rapamycin (mTOR) is closely associated with the risk of AS. The mTOR signaling pathway contributes to AS progression through regulating autophagy, cell senescence, immune response, and lipid metabolism. Botanical drugs and their functional compounds have shown anti-AS effects by modulating the activity of the mTOR signaling pathway. This review summarizes the pathogenesis of AS based on the mTOR signaling pathway and recent advances in natural compounds to inhibit the mTOR signaling pathway and delay AS development, providing a new perspective on the mechanisms and precision treatments of AS.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Neslihan Pinar Ozates, Fatma Sogutlu, Ferzan Lerminoglu, Busra Demir, Cumhur Gunduz, Behrouz Shademan, Cigir Biray Avci
Summary: Breast cancer is the most common cancer in women and aberrations in the PI3K/AKT/mTOR pathway present in more than 70% of breast cancer cases have become a therapeutic target. AZD3463, as an anti-cancer agent, induces apoptosis and autophagy in breast cancer cells, reducing cell survival and proliferation. The combination of rapamycin and AZD3463 can increase the expression of certain genes related to apoptosis and decrease genes associated with cell survival, reducing resistance to treatment and leading to cancer cell apoptosis.
Editorial Material
Cell Biology
Anais Franco-Romero, Jean Philippe Leduc-Gaudet, Sabah N. A. Hussain, Gilles Gouspillou, Marco Sandri
Summary: Skeletal muscles play key roles in various physiological processes, and autophagy is crucial for muscle mass, function, and integrity. In this study, a novel gene called PHAF1/MYTHO was identified as a regulator of autophagy and muscle integrity. MYTHO/PHAF1 is upregulated in muscle atrophy conditions and downregulation of its expression can prevent muscle atrophy triggered by fasting, denervation, cachexia, and sepsis.
Review
Biochemistry & Molecular Biology
Seo Hyeong Park, Won Hoon Choi, Min Jae Lee
Summary: mTOR, a mechanistic target, plays a crucial role in regulating cellular homeostasis and cell growth, including autophagy and proteasome activity. Inhibition of mTORC1 can induce autophagy, while proteasomes provide amino acids necessary for protein synthesis. Understanding the connection between mTORC1 activity and proteasome function is important for the evaluation of mTORC1 inhibitors as therapeutic treatments.
Article
Orthopedics
Yanghua Tang, Yafeng Mo, Dawei Xin, Zhenfei Xiong, Linru Zeng, Gan Luo, Yanguang Cao
Summary: The study revealed that beta-ecdysterone may promote fracture healing by enhancing autophagy and inhibiting the PI3K/AKT/mTOR signaling pathway. Experimental results showed that beta-ecdysterone significantly increased alkaline phosphatase activity and RunX2 expression in fractured osteoblasts, while suppressing the apoptotic rate.
JOURNAL OF ORTHOPAEDIC SURGERY AND RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ingrid Vargova, Lucia Machova Urdzikova, Kristyna Karova, Barbora Smejkalova, Tolga Sursal, Veronika Cimermanova, Karolina Turnovcova, Chirag D. Gandhi, Meena Jhanwar-Uniyal, Pavla Jendelova
Summary: The study found that partial neuroprotection and recovery after traumatic spinal cord injury can be achieved by inhibiting the mTOR pathway, with the second-generation inhibitor pp242 showing different effects compared to rapamycin (RAPA) in terms of inflammatory responses and autophagy.
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)
Review
Immunology
Anne E. O'Shea, Franklin A. Valdera, Daniel Ensley, Todd R. Smolinsky, Jessica L. Cindass, Phillip M. Kemp Bohan, Annelies T. Hickerson, Elizabeth L. Carpenter, Patrick M. McCarthy, Alexandra M. Adams, Timothy J. Vreeland, Guy T. Clifton, George E. Peoples
Summary: Rapamycin inhibits mTOR signaling, exhibiting both immunosuppressive and immunostimulatory effects on innate and adaptive immune responses. The dose and administration schedule play a crucial role in modulating rapamycin's immunologic effects.
CLINICAL IMMUNOLOGY
(2022)
Editorial Material
Cell Biology
Yuchen Lei, Daniel J. Klionsky
Summary: VCP, a conserved ATPase, regulates autophagy initiation by stabilizing BECN1 and enhancing phosphati-dylinositol 3-kinase (PtdIns3K) complex assembly, in addition to its roles in autophagosome maturation.
Article
Neurosciences
Francesca Biagioni, Roberta Celli, Filippo Sean Giorgi, Ferdinando Nicoletti, Francesco Fornai
Summary: This article discusses the novel role of the piriform cortex in epileptic seizures and its modulation of AMPA receptors under the influence of mTORC1. The results show that the mTORC1 inhibitor rapamycin can mitigate the duration, severity, and brain damage of seizures.
CURRENT NEUROPHARMACOLOGY
(2022)
Article
Cell Biology
Sanjar Batirovich Madrakhimov, Jin Young Yang, Jin Ha Kim, Jung Woo Han, Tae Kwann Park
Summary: The study suggests that mTOR signaling may play a crucial role in neuronal cell death in diabetic retinopathy. Diabetes-induced neurodegeneration is characterized by an increase in apoptotic markers and autophagic proteins, which can be reduced by glycemic control. Insulin-independent glycemic control restores mTOR pathway activity and decreases neuroretinal autophagic and apoptotic proteins in diabetic mice.
CELL COMMUNICATION AND SIGNALING
(2021)
