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
Dermatology
Shenyu Zhu, Wenbo Yu, Jianfeng Gao, Jianxian Xiong
Summary: A meta-analysis showed that heart transplant recipients on mammalian target of rapamycin inhibitors (MTRIs) had a significantly higher frequency of wound complications (WCs) compared to those on control.
INTERNATIONAL WOUND JOURNAL
(2023)
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
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
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)
Review
Immunology
Lu Zhang, Cui Jiao, Lingjuan Liu, Aiping Wang, Li Tang, Yi Ren, Peng Huang, Jie Xu, Dingan Mao, Liqun Liu
Summary: NLRC5, the largest member of the NLR family, plays a significant role in inflammatory processes, angiogenesis, immunity, and apoptosis by regulating various signaling pathways. Recent studies have also linked NLRC5 with neuronal development and CNS diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Dermatology
Mirit Gluck, Emmilia Hodak, Batya Davidovici
Summary: Immunosuppressants are crucial for graft survival in solid-organ transplant recipients, but they can lead to an increased incidence of nonmelanoma skin cancers. A retrospective study showed that mammalian target of rapamycin inhibitors (mTORi) have a sustained effectiveness in reducing the occurrence of nonmelanoma skin cancers.
DERMATOLOGIC THERAPY
(2022)
Article
Rheumatology
Ecem Sevim, Salma Siddique, Madhavi Latha S. Chalasani, Susan Chyou, William D. Shipman, Orla O'Shea, Joanna Harp, Oral Alpan, Stephane Zuily, Theresa T. Lu, Doruk Erkan
Summary: This study investigated the activation of the mammalian target of rapamycin (mTOR) in the skin of patients with livedo and antiphospholipid antibodies (aPL). The results showed increased mTOR activity in the skin of aPL-positive patients, which may have implications for further research on the mTOR pathway in these patients.
JOURNAL OF RHEUMATOLOGY
(2022)
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
Biochemistry & Molecular Biology
Divya M. Teli, Anuradha K. Gajjar
Summary: Elevated glucose level due to β-cell dysfunction is a key marker of Type-II diabetes. GSK-3, an enzyme involved in glycogen metabolism control, has been explored for its potential as a target for diabetes treatment. This review article examines the structural analysis and molecular modeling of GSK-3, as well as advancements in the development of GSK-3 inhibitors as potential therapeutics for Type II diabetes.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Physiology
Bahetiyaer Huwatibieke, Wenzhen Yin, Lingchao Liu, Yuxin Jin, Xinxin Xiang, Jingyan Han, Weizhen Zhang, Yin Li
Summary: The study demonstrates that the mTOR signaling pathway affects the transformation of adipocytes by regulating mitochondrial quality control in brown adipocytes. Activation of mTOR signaling inhibits the mitochondrial quality control and promotes the transformation from brown to white adipocytes, while inhibition of mTOR signaling enhances mitochondrial quality control and inhibits the phenotypic shift.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Naser-Aldin Lashgari, Nazanin Momeni Roudsari, Saeideh Momtaz, Negar Ghanaatian, Parichehr Kohansal, Mohammad Hosein Farzaei, Khashayar Afshari, Amirhossein Sahebkar, Amir Hossein Abdolghaffari
Summary: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders with unclear etiology. Studies suggest that inhibition of the mTOR signaling pathway may help reduce the inflammatory processes and cytokines involved in IBD.
CURRENT MEDICINAL CHEMISTRY
(2021)
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
Cardiac & Cardiovascular Systems
Jessica Selig, H. Viviana Krug, Caroline Kueppers, D. Margriet Ouwens, Felix A. Kraft, Elena Adler, Sebastian J. Bauer, Artur Lichtenberg, Payam Akhyari, Mareike Barth
Summary: Diabetes and its key determinants, insulin resistance and hyperglycemia, contribute to calcific aortic valve disease (CAVD) by causing alterations in valvular interstitial cells (VIC) and extracellular matrix remodeling. The mTOR signaling pathway plays a crucial role in this process.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Immunology
Naser-Aldin Lashgari, Nazanin Momeni Roudsari, Seyed Saeed Tamehri Zadeh, Saeideh Momtaz, Mitra Abbasifard, Zeljko Reiner, Amir Hossein Abdolghaffari, Amirhossein Sahebkar
Summary: This critical review examines the critical role of inflammation in various diseases and the potential of statins as inhibitors of the mTOR pathway to regulate inflammation. By collecting data from clinical, in vivo, and in vitro studies, the researchers summarize the beneficial effects of statins on inflammatory diseases.
INFLAMMOPHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Anita R. Patel, Henriette Frikke-Schmidt, Olivier Bezy, Paul Sabatini, Nikolaj Rittig, Niels Jessen, Martin G. Myers, Randy J. Seeley
Summary: The study found that Lipopolysaccharide (LPS) can increase levels of GDF15 in mice, rats, and humans, but GDF15 is not necessary for inducing anorexia and weight loss in response to moderate systemic infection.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Neurosciences
Nadia Di Franco, Guillaume Drutel, Valerie Roullot-Lacarriere, Francisca Julio-Kalajzic, Valerie Lalanne, Agnes Grel, Thierry Leste-Lasserre, Isabelle Matias, Astrid Cannich, Delphine Gonzales, Vincent Simon, Daniela Cota, Giovanni Marsicano, Pier Vincenzo Piazza, Monique Vallee, Jean-Michel Revest
Summary: Down syndrome is the most common genetic cause of mental retardation and is associated with learning and memory deficits. The overexpression of genes and alterations in protein synthesis due to the triplication of chromosome 21 seem to play a major role in this syndrome. The upregulation of the endocannabinoid system, especially the cannabinoid type-1 receptor, may contribute to the learning and memory impairments in Down syndrome. The expression pattern of ECS components, particularly CB1, is altered in Ts65Dn mice, highlighting a complex regulation that could lead to new therapeutic solutions for this syndrome.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2022)
Article
Nutrition & Dietetics
Raphael Enaud, Sophie Cambos, Esther Viaud, Erwan Guichoux, Emilie Chancerel, Aline Marighetto, Nicole Etchamendy, Samantha Clark, Kamel Mohammedi, Daniela Cota, Laurence Delhaes, Blandine Gatta-Cherifi
Summary: This study found that bariatric surgery in obese patients can improve memory function and gut microbiota, with changes in the microbiota associated with improvements in cognitive function. The complex gut-brain-axis evolves after bariatric surgery, with specific microbial changes linked to either verbal or working memory improvements.
Article
Multidisciplinary Sciences
Gianluca Sighinolfi, Samantha Clark, Landry Blanc, Daniela Cota, Boutayna Rhourri-Frih
Summary: Studies have shown that obesity is closely related to changes in brain structure and function. Through experiments on mice, it was found that a high-fat diet can rapidly alter the brain lipidome, with some changes persisting even after weight loss.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Nicolas Saucisse, Wilfrid Mazier, Vincent Simon, Elke Binder, Caterina Catania, Luigi Bellocchio, Roman A. Romanov, Stephane Leon, Isabelle Matias, Philippe Zizzari, Carmelo Quarta, Astrid Cannich, Kana Meece, Delphine Gonzales, Samantha Clark, Julia M. Becker, Giles S. H. Yeo, Xavier Fioramonti, Florian T. Merkle, Sharon L. Wardlaw, Tibor Harkany, Federico Massa, Giovanni Marsicano, Daniela Cota
Summary: Blocking the energy sensor mTORC1 in POMC neurons can mimic a cellular negative energy state, leading to hyperphagia. The functional specificity of the GABA and glutamate subpopulations in POMC neurons relies on the activity of mTORC1.
Article
Medicine, Research & Experimental
Antonio J. L. Lopez-Gambero, Beatriz Pacheco-Sanchez, Cristina Rosell-Valle, Dina Medina-Vera, Juan Antonio Navarro, Maria del Mar Fernandez-Arjona, Marialuisa de Ceglia, Carlos Sanjuan, Vincent Simon, Daniela Cota, Patricia Rivera, Fernando Rodriguez de Fonseca, Juan Suarez
Summary: The occurrence and progression of hypothalamic dysfunction, insulin resistance, and weight loss are associated with the cognitive decline in sporadic Alzheimer's Disease (AD) with sex differences. This study found that oral supplementation with insulin-sensitizing D-Chiro-inositol (DCI) partially restored energy balance and improved metabolic disorders in a mouse model of AD.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Medicine, Research & Experimental
Ki-Suk Kim, Bailey Ce Peck, Yu-Han Hung, Kieran Koch-Laskowski, Landon Wood, Priya H. Dedhia, Jason R. Spence, Randy J. Seeley, Praveen Sethupathy, Darleen A. Sandoval
Summary: This study found that vertical sleeve gastrectomy (VSG) increases the number of hormone-secreting enteroendocrine cells (EECs) in the intestine through bile acid signaling, which drives intestinal stem cell fate towards EEC differentiation.
Article
Endocrinology & Metabolism
Emilie Pupier, Alicia Santos, Nicole Etchamendy, Aurelie Lavielle, Amandine Ferriere, Aline Marighetto, Eugenia Resmini, Daniela Cota, Susan M. Webb, Antoine Tabarin
Summary: Cognitive impairments and altered quality of life may persist in patients with long-term remission of Cushing's disease, even in the absence of other comorbidities. Memory tests revealed similar performance between patients and controls, but patients had worse quality of life despite no depression or residual clinical symptoms of Cushing's disease.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Hugo Martin, Sebastien Bullich, Maud Martinat, Mathilde Chataigner, Mathieu Di Miceli, Vincent Simon, Samantha Clark, Jasmine Butler, Mareike Schell, Simran Chopra, Francis Chaouloff, Andre Kleinridders, Daniela Cota, Philippe De Deurwaerdere, Luc Penicaud, Sophie Laye, Bruno P. Guiard, Xavier Fioramonti
Summary: Insulin directly modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and control emotional behaviors. However, in T2D animal models, the anxiolytic effect of intranasal insulin and the response of 5-HT neurons to insulin are both blunted.
MOLECULAR PSYCHIATRY
(2022)
Article
Cell Biology
Antonio C. Pagano Zottola, Ilenia Severi, Astrid Cannich, Philippe Ciofi, Daniela Cota, Giovanni Marsicano, Antonio Giordano, Luigi Bellocchio
Summary: By activating the CB1 receptor, cannabinoids regulate mitochondrial physiology and energy metabolism in adipocytes through intracellular signaling pathways.
Article
Neurosciences
Marie Lods, Pierre Mortessagne, Emilie Pacary, Geoffrey Terral, Fanny Farrugia, Wilfrid Mazier, Nuria Masachs, Vanessa Charrier, Daniela Cota, Guillaume Ferreira, Djoher Nora Abrous, Sophie Tronel
Summary: Adult neurogenesis in the hippocampus plays a crucial role in memory processes, but its direct impact on memory performance remains uncertain. This study developed a chemogenetic method to selectively activate specific populations of adult-born neurons, and demonstrated that this activation can improve the accuracy and strength of remote memory in rats. These findings suggest that stimulating adult-born neuron activity may counteract the natural decline of memory traces over time, offering new potential for treating memory problems.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Physiology
Anita R. Patel, Henriette Frikke-Schmidt, Paul V. Sabatini, Alan C. Rupp, Darleen A. Sandoval, Martin G. Myers, Randy J. Seeley
Summary: Deoxynivalenol (DON), a mycotoxin contaminating grain, induces nausea, emesis, and anorexia. The study found that GLP-1 is not necessary for DON-induced effects on food intake and visceral illness. Additionally, the study showed that the calcium-sensing receptor (CaSR) on GFRAL neurons may play a role in DON signaling, but neither GLP-1 signaling nor GFRAL signaling and neurons are required for DON-induced visceral illness or anorexia.
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
(2023)
Editorial Material
Endocrinology & Metabolism
Samuel Klein, Randy J. Seeley
Summary: Many individuals with obesity and type 2 diabetes experience diabetes remission after Roux-en-Y gastric bypass surgery, but there is disagreement regarding the underlying mechanisms. We present our perspective on conflicting datasets suggesting that the remission could be attributed solely to weight loss or weight loss-independent factors.
Article
Biology
Carlos Sepulveda, Juan Manuel Rodriguez, Matias Monsalves-Alvarez, Camila Donoso-Barraza, Francisco de la Fuente, Isabelle Matias, Thierry Leste-Lasserre, Philippe Zizzari, Eugenia Morselli, Daniela Cota, Miguel Llanos, Rodrigo Troncoso
Summary: The endocannabinoid system (ECS) regulates energy metabolism and is involved in the pathogenesis of metabolic diseases. Autophagy is associated with various cellular processes and its deregulation is linked to diseases. This study found that the CB1 receptor controls autophagy in the skeletal muscle of both lean and obese mice.
BIOLOGICAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Camille Allard, Daniela Cota, Carmelo Quarta
Summary: The use of GLP-1 receptor-based multi-agonists shows promise in treating type 2 diabetes and obesity, but there are knowledge gaps regarding their mechanisms and potential adverse effects. This review critically analyzes the benefits and risks of these drugs in the management of obesity and diabetes, and explores new potential applications of GLP-1 pharmacology beyond metabolic diseases.