Article
Multidisciplinary Sciences
Delong Meng, Qianmei Yang, Mi-Hyeon Jeong, Adna Curukovic, Shweta Tiwary, Chase H. Melick, Tshering D. Lama-Sherpa, Huanyu Wang, Mariela Huerta-Rosario, Greg Urquhart, Lauren G. Zacharias, Cheryl Lewis, Ralph J. DeBerardinis, Jenna L. Jewell
Summary: SNAT7 activates mTORC1 by mediating the macropinocytosis of extracellular proteins independently of Rag GTPase. It plays a crucial regulatory role in mTORC1 activation and is essential for sustaining KRAS-driven pancreatic cancer cell growth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Zixi Wang, Di Guan, Jianxin Huo, Subhra K. Biswas, Yuhan Huang, Yuansheng Yang, Shengli Xu, Kong-Peng Lam
Summary: The study demonstrates that IL-10 upregulates both glycolysis and oxidative phosphorylation in human NK cells, crucial for their enhanced effector functions. Mechanistically, it is revealed that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Agnieszka A. Gorska, Clara Sandmann, Eva Riechert, Christoph Hofmann, Ellen Malovrh, Eshita Varma, Vivien Kmietczyk, Julie Oelschlaeger, Lonny Juergensen, Verena Kamuf-Schenk, Claudia Stroh, Jennifer Furkel, Mathias H. Konstandin, Carsten Sticht, Etienne Boileau, Christoph Dieterich, Norbert Frey, Hugo A. Katus, Shirin Doroudgar, Mirko Voelkers
Summary: The study reveals the role of mTOR in pathological remodeling of the heart, showing that it protects cardiomyocytes by controlling the translation of specific genes, with Cand2 being a mTOR-regulated protective gene.
Article
Biochemistry & Molecular Biology
Liangfang Yao, Yang Xuan, Haiyang Zhang, Bo Yang, Xinglong Ma, Tianzhen Wang, Tianyuan Meng, Wenshe Sun, Haibin Wei, Xueqing Ma, Robb Moses, Jianru Xiao, Pei Zhang, Chao Ge, Jinjun Li, Lei Li, Xiaotao Li, Jinbao Li, Bianhong Zhang
Summary: The study has identified the REG gamma-PP2Ac-PRAS40 axis as a new layer in regulating mTORC1 activity and downstream glycolytic alterations during HCC development, highlighting the REG gamma-proteasome as a potential target for personalized HCC therapy.
Article
Endocrinology & Metabolism
Gommaar D'Hulst, Evi Masschelein, Katrien De Bock
Summary: This study found that exercise enhances sensitivity of mTORC1 to leucine, which can last at least 48 hours. Exercise promotes the expression of amino acid transporters and uptake of leucine into muscles, leading to increased expression of genes involved in leucine sensing and amino acid metabolism. Additionally, exercise increased ATF4 protein expression.
MOLECULAR METABOLISM
(2022)
Article
Clinical Neurology
Sarah Gourmaud, David A. Stewart, David J. Irwin, Nicholas Roberts, Aaron J. Barbour, Grace Eberwine, William T. O'Brien, Robert Vassar, Delia M. Talos, Frances E. Jensen
Summary: Seizures are more common in Alzheimer's disease patients, and they exacerbate the progression of the disease by increasing amyloid-beta and tau pathology and activating the mTOR pathway. The mTOR inhibitor rapamycin can rescue memory deficits and attenuate Alzheimer's disease neuropathology.
Article
Environmental Sciences
Yuexin Wei, Yu Zhou, Chunlan Long, Huan Wu, Yifan Hong, Yan Fu, Junke Wang, Yuhao Wu, Lianju Shen, Guanghui Wei
Summary: Exposure to polystyrene microplastics (PS-MPs) has been found to decrease sperm quality and quantity in male Balb/c mice. This is likely due to the disruption of blood-testis barrier (BTB) integrity, induced by PS-MPs causing cytoskeleton disorganization and imbalanced mTORC1 and mTORC2 activities via increased ROS levels.
ENVIRONMENTAL POLLUTION
(2021)
Review
Physiology
Angelia Szwed, Eugene Kim, Estela Jacinto
Summary: Cells metabolize nutrients for growth and proliferation, with mTOR playing a key role in integrating growth and metabolism through the protein complexes mTORC1 and mTORC2. Study of mTORC1 and mTORC2 has expanded our understanding of cellular metabolism regulation and functions.
PHYSIOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Danilo De Gregorio, Jelena Popic, Justine P. Enns, Antonio Inserra, Agnieszka Skalecka, Athanasios Markopoulos, Luca Posa, Martha Lopez-Canul, He Qianzi, Christopher K. Lafferty, Jonathan P. Britt, Stefano Comai, Argel Aguilar-Valles, Nahum Sonenberg, Gabriella Gobbi
Summary: Clinical studies have shown that LSD can enhance empathy and social behavior in humans. This study in male mice found that LSD promotes social behavior by potentiating glutamatergic neurotransmission in the medial prefrontal cortex through the 5-HT2A/AMPA receptors and mTOR signaling. The results suggest that activating these pathways with psychedelic drugs could be explored for treating mental disorders characterized by social behavior impairments.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, Research & Experimental
Dapeng Li, Anjiang Sun, Liang Zhang, Zhao Ding, Fangzheng Yi, Xue Yang, Zixi Wang, Xu Chen, Weiwei Liu, Shixian Liu, Hailong Shen, Manli Miao, Ling Zhang, Ping Liu, Yuchen Liu, Shihong Su, Hailiang Huang, Can Huang, Zhongdong Hu, Hongbing Zhang, Xiaojun Zha, Yehai Liu
Summary: We established a novel LSCC cell line and identified ITGA5 as a functional downstream effector of mTORC1 in LSCC progression. Elevated ITGA5 promotes LSCC progression through augmentation of EFNB2. Clinical data analysis showed that the activation of the mTORC1-ITGA5-EFNB2 pathway is associated with malignant progression and poor prognosis in LSCC patients. Inhibition of ITGA5 significantly increased the sensitivity of LSCC cells to CDDP.
Article
Clinical Neurology
Jeffrey D. Calhoun, Miriam C. Aziz, Hannah C. Happ, Jonathan Gunti, Colleen Gleason, Najma Mohamed, Kristy Zeng, Meredith Hiller, Emily Bryant, Divakar S. Mithal, Irena Bellinski, Lisa Kinsley, Mona Grimmel, Eva M. C. Schwaibold, Constance Smith-Hicks, Anna Chassevent, Marcello Scala, Andrea Accogli, Annalaura Torella, Pasquale Striano, Valeria Capra, Lynne M. Bird, Issam Ben-Sahra, Nina Ekhilevich, Tova Hershkovitz, Karin Weiss, John Millichap, Elizabeth E. Gerard, Gemma L. Carvill
Summary: Biallelic pathogenic variants in SZT2 are associated with a neurodevelopmental disorder characterized by early-onset epilepsy, developmental delay, macrocephaly, and corpus callosum abnormalities. A novel assay was developed to identify SZT2 variants and reclassify variants of uncertain significance, leading to the identification of a recurrent loss-of-function variant and refinement of the phenotypic spectrum. This approach has wider applicability to other mTORopathies.
Article
Medicine, Research & Experimental
Zhili Deng, Mengting Chen, Yingzi Liu, San Xu, Yuyan Ouyang, Wei Shi, Dan Jian, Ben Wang, Fangfen Liu, Jinmao Li, Qian Shi, Qinqin Peng, Ke Sha, Wenqin Xiao, Tangxiele Liu, Yiya Zhang, Hongbing Zhang, Qian Wang, Lunquan Sun, Hongfu Xie, Ji Li
Summary: The study demonstrates that mTORC1 signaling is hyperactivated in the skin of rosacea patients and mouse model, blocking mTORC1 signaling can alleviate rosacea symptoms, while its hyperactivation can worsen the condition.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Yingjun Cai, Kangcheng Liu, Pengfei Wu, Ruolan Yuan, Fei He, Jing Zou
Summary: This study demonstrates the importance of EIF4EBP in the development of cataract through a Mendelian randomization analysis. It suggests a potential causal association between the mTORC1/EIF4EBP axis and cataract formation.
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
Biochemistry & Molecular Biology
Asmaa Y. Abuhamad, Nurul Nadia Mohamad Zamberi, Sakari Vanharanta, Siti Nur Hasanah Mohd Yusuf, M. Aiman Mohtar, Saiful Effendi Syafruddin
Summary: This study found that clear cell renal cell carcinoma (ccRCC) cells are able to secrete PDGFB, which can activate the mTORC1 signaling pathway and promote the development of ccRCC. The level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Reintroduction of either KLF6 or PDGFB sustained mTORC1 signaling activity in KLF6-targeted ccRCC cells. Conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. Cancer cell-derived PDGFB can mediate mTORC1 signaling pathway activation in ccRCC, further solidifying the association between the KLF6-PDGFB axis and mTORC1 signaling pathway activity in ccRCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Canan G. Nebigil, Laurent Desaubry
TRENDS IN CARDIOVASCULAR MEDICINE
(2019)
Article
Oncology
Marine F. Garrido, Nicolas J-P Martin, Matthieu Bertrand, Catherine Gaudin, Frederic Commo, Nassif El Kalaany, Nader Al Nakouzi, Ladan Fazli, Elaine Del Nery, Jacques Camonis, Franck Perez, Stephanie Lerondel, Alain Le Pape, Daniel Compagno, Martin Gleave, Yohann Loriot, Laurent Desaubry, Stephan Vagner, Karim Fizazi, Anne Chauchereau
CLINICAL CANCER RESEARCH
(2019)
Article
Cell Biology
Chaojun Yan, Longlong Gong, Li Chen, Meng Xu, Hussein Abou-Hamdan, Mingliang Tang, Laurent Desaubry, Zhiyin Song
Article
Chemistry, Medicinal
Sabria Elderwish, Anais Audebrand, Canan G. Nebigil, Laurent Desaubry
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Oncology
Hafidha Bentayeb, Marine Aitamer, Barbara Petit, Lydie Dubanet, Sabria Elderwish, Laurent Desaubry, Armand de Gramont, Eric Raymond, Agnes Olivrie, Julie Abraham, Marie-Odile Jauberteau, Danielle Troutaud
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2019)
Article
Toxicology
Fathi Emhemmed, Sarah Ali Azouaou, Sarah Hassan, Ray Lefevbre, Laurent Desaubry, Christian D. Muller, Guy Fuhrmann
TOXICOLOGY IN VITRO
(2019)
Article
Chemistry, Multidisciplinary
Dong Wang, Xinyue Ma, Linru Dong, Hairong Feng, Peng Yu, Laurent Desaubry
FRONTIERS IN CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Dong Wang, Redouane Tabti, Sabria Elderwish, Hussein Abou-Hamdan, Amel Djehal, Peng Yu, Hajime Yurugi, Krishnaraj Rajalingam, Canan G. Nebigil, Laurent Desaubry
CELLULAR AND MOLECULAR LIFE SCIENCES
(2020)
Article
Multidisciplinary Sciences
Shensi Shen, Sara Faouzi, Amandine Bastide, Sylvain Martineau, Helene Malka-Mahieu, Yu Fu, Xiaoxiao Sun, Christine Mateus, Emilie Routier, Severine Roy, Laurent Desaubry, Fabrice Andre, Alexander Eggermont, Alexandre David, Jean-Yves Scoazec, Stephan Vagner, Caroline Robert
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Xin Jin, Jianling Xie, Michael Zabolocki, Xuemin Wang, Tao Jiang, Dong Wang, Laurent Desaubry, Cedric Bardy, Christopher G. Proud
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Cell Biology
Hajime Yurugi, Yinyin Zhuang, Farid Siddiqui, Hong Liang, Sebastian Rosigkeit, Yongpeng Zeng, Hussein Abou-Hamdan, Ernesto Bockamp, Yong Zhou, Daniel Abankwa, Wenting Zhao, Laurent Desaubry, Krishnaraj Rajalingam
JOURNAL OF CELL SCIENCE
(2020)
Article
Chemistry, Organic
Dong Wang, Yuanyang Jiang, Linru Dong, Gaoyu Li, Baoying Sun, Laurent Desaubry, Peng Yu
JOURNAL OF ORGANIC CHEMISTRY
(2020)
Article
Chemistry, Multidisciplinary
Dong Wang, Yu Fan, Peng Yu, Laurent Desaubry
CHEMICAL COMMUNICATIONS
(2020)
Review
Cardiac & Cardiovascular Systems
Anais Audebrand, Laurent Desaubry, Canan G. Nebigil
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2020)
Meeting Abstract
Biochemistry & Molecular Biology
Dakota N. Jackson, Hussein Abou-Hamdan, Beth N. Cook, Lauent Desaubry, Rhonda F. Souza, Arianne L. Theiss
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
