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
Cell Biology
Anna Rocchi, Emanuele Carminati, Antonio De Fusco, Jagoda Aleksandra Kowalska, Thomas Floss, Fabio Benfenati
Summary: Research shows that REST plays a crucial role in preventing the senescence phenotype in neurons, and its deficiency leads to impaired autophagy, loss of proteostasis, increased oxidative stress, and elevated cell death rate. Restoring autophagy can effectively reverse the primary hallmarks of cell senescence.
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
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)
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.
Review
Pharmacology & Pharmacy
Alexander B. Pupyshev, Tatyana P. Klyushnik, Anna A. Akopyan, Sandeep Kumar Singh, Maria A. Tikhonova
Summary: Trehalose is a promising approach for the treatment of neurodegenerative diseases through its induction of autophagy. It has anti-inflammatory, antioxidant, and neuroprotective effects, reducing the accumulation of abnormal proteins. Trehalose activates lysosome and autophagosome biogenesis pathways. However, further research is needed to understand its pharmacodynamics. Trehalose has demonstrated potential in treating diseases such as Alzheimer's, Parkinson's, and Huntington's in animal models.
PHARMACOLOGICAL RESEARCH
(2022)
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
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)
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)
Article
Reproductive Biology
Lian Cai, Junchul David Yoon, Seon-Ung Hwang, Joohyeong Lee, Eunhye Kim, Mirae Kim, Saang-Yoon Hyun, Hyerin Choi, Dongjin Oh, Yubyeol Jeon, Sang-Hwan Hyun
Summary: This study reveals that trehalose plays a role as an autophagy activator in porcine oocyte maturation. The mechanisms involved differ between cumulus cells and oocytes. In cumulus cells, trehalose activates autophagy by improving lysosomal function and autophagic clearance via PI3K/Akt inhibition. In oocytes, trehalose activates autophagy via induction of VPS34, which affects autophagosome formation, while ensuring the precise meiotic process through Akt inhibition and mTOR activation.
BIOLOGY OF REPRODUCTION
(2022)
Article
Biology
Afsal Kolloli, Ranjeet Kumar, Pooja Singh, Anshika Narang, Gilla Kaplan, Alex Sigal, Selvakumar Subbian
Summary: The study found that infection with Mycobacterium tuberculosis aggregates in rabbit lungs resulted in significantly higher bacterial loads, disease scores, lesion size, and structure compared to infection with single bacilli. Differences in immune cell distribution and activation were observed between the two groups of infected animals. Aggregates of bacteria exacerbate lung inflammation and host cell death, thereby worsening disease pathology.
COMMUNICATIONS BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Guoli Shi, Abhilash I. Chiramel, Tiansheng Li, Kin Kui Lai, Adam D. Kenney, Ashley Zani, Adrian C. Eddy, Saliha Majdoul, Lizhi Zhang, Tirhas Dempsey, Paul A. Beare, Swagata Kar, Jonathan W. Yewdell, Sonja M. Best, Jacob S. Yount, Alex A. Compton
Summary: The use of rapalog drugs increases susceptibility to SARS-CoV-2 infection in immunocompromised individuals by promoting virus entry into cells and inhibiting the cell-intrinsic immune response.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Behavioral Sciences
Alexander B. Pupyshev, Victor M. Belichenko, Michael V. Tenditnik, Alim A. Bashirzade, Nina I. Dubrovina, Marina V. Ovsyukova, Anna A. Akopyan, Larisa A. Fedoseeva, Tatiana A. Korolenko, Tamara G. Amstislavskaya, Maria A. Tikhonova
Summary: By comparing the effects of rapamycin and trehalose in the treatment of Alzheimer's disease, it was found that trehalose can effectively induce autophagy and improve AD-related behavioral and neuronal deficits, with the best outcomes achieved with the combined treatment.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2022)
Article
Chemistry, Medicinal
Keiko Nishizawa, Kenta Teruya, Ayumi Oguma, Yuji Sakasegawa, Hermann Schatzl, Sabine Gilch, Katsumi Doh-ura
JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Article
Pharmacology & Pharmacy
Dalia H. Abdelaziz, Basant A. Abduirahman, Sabine Gilch, Hermann M. Schatzl
CURRENT OPINION IN PHARMACOLOGY
(2019)
Article
Cardiac & Cardiovascular Systems
Hamood N. Al Kindi, Mahmoud Shehata, Ayman M. Ibrahim, Mohamed Roshdy, Walid Simry, Yasmine Aguib, Magdi H. Yacoub
ANNALS OF THORACIC SURGERY
(2020)
Article
Genetics & Heredity
Xiaolei Zhang, Roddy Walsh, Nicola Whiffin, Rachel Buchan, William Midwinter, Alicja Wilk, Risha Govind, Nicholas Li, Mian Ahmad, Francesco Mazzarotto, Angharad Roberts, Pantazis I. Theotokis, Erica Mazaika, Mona Allouba, Antonio de Marvao, Chee Jian Pua, Sharlene M. Day, Euan Ashley, Steven D. Colan, Michelle Michels, Alexandre C. Pereira, Daniel Jacoby, Carolyn Y. Ho, Iacopo Olivotto, Gunnar T. Gunnarsson, John L. Jefferies, Chris Semsarian, Jodie Ingles, Declan P. O'Regan, Yasmine Aguib, Magdi H. Yacoub, Stuart A. Cook, Paul J. R. Barton, Leonardo Bottolo, James S. Ware
Summary: The disease-specific variant classifier CardioBoost demonstrates superior performance in accurately distinguishing disease-causing from benign variants, prioritizing disease-associated variants, and stratifying patient outcomes in inherited cardiac conditions. Its high global discrimination accuracy and improved confidence in variant classification suggest broad opportunities for enhanced pathogenicity prediction through disease specificity.
GENETICS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ayman M. Ibrahim, Mohamed Roshdy, Sara Elshorbagy, Mohammed Hosny, Sarah Halawa, Dina Yehia, Hasnaa A. Elfawy, Ahmed Eldessouki, Faisal Mohamed, Amany Ellithy, Mohamed Abdelfattah, Amr Elsawy, Mohamed Elkhatib, Mona Allouba, Ahmed Elguindy, Yasmine Aguib, Magdi Yacoub
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Genetics & Heredity
Yasmine Aguib, Mona Allouba, Alaa Afify, Sarah Halawa, Mohamed El-Khatib, Marina Sous, Aya Galal, Eslam Abdelrahman, Nairouz Shehata, Amr El Sawy, Mohamed Elmaghawry, Shehab Anwer, Omnia Kamel, Wesam El Mozy, Hadir Khedr, Ahmed Kharabish, Nagwa Thabet, Pantazis Theotokis, Rachel Buchan, Risha Govind, Nicola Whiffin, Roddy Walsh, Heba Aguib, Ahmed Elguindy, Declan P. O'Regan, Stuart A. Cook, Paul J. Barton, James S. Ware, Magdi Yacoub
NPJ GENOMIC MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Cristobal Marrero-Winkens, Charu Sankaran, Hermann M. Schatzl
Article
Genetics & Heredity
Francesco Mazzarotto, Megan H. Hawley, Matteo Beltrami, Leander Beekman, Antonio de Marvao, Kathryn A. McGurk, Ben Statton, Beatrice Boschi, Francesca Girolami, Angharad M. Roberts, Elisabeth M. Lodder, Mona Allouba, Soha Romeih, Yasmine Aguib, A. John Baksi, Antonis Pantazis, Sanjay K. Prasad, Elisabetta Cerbai, Magdi H. Yacoub, Declan P. O'Regan, Stuart A. Cook, James S. Ware, Birgit Funke, Iacopo Olivotto, Connie R. Bezzina, Paul J. R. Barton, Roddy Walsh
Summary: Left ventricular noncompaction (LVNC) shows significant genetic overlap with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), but also has distinct noncompaction and arrhythmia etiologies. These results will enhance the application of LVNC genetic testing and aid in distinguishing pathological from physiological noncompaction.
GENETICS IN MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Hamood N. Al Kindi, Ayman M. Ibrahim, Mohamed Roshdy, Besra S. Abdelghany, Dina Yehia, Ahmed Nageeb Masoud, Walid Simry, Yasmine Aguib, Magdi H. Yacoub
Summary: This study investigated the clinical features and genetic analysis of patients with tuberous sclerosis complex presenting with large rhabdomyoma tumors, as well as the potential role of autophagy and apoptosis in tumor pathogenesis. Results showed increased expression of autophagic and apoptotic markers in tumor cells compared to normal tissue, with patients carrying pathogenic mutations in the TSC-2 gene requiring urgent intervention. Future studies may lead to personalized treatment for cardiac rhabdomyoma.
CARDIOLOGY IN THE YOUNG
(2021)
Review
Biochemistry & Molecular Biology
Maria Immaculata Arifin, Samia Hannaoui, Sheng Chun Chang, Simrika Thapa, Hermann M. Schatzl, Sabine Gilch
Summary: Chronic wasting disease (CWD) is a prion disease found in both free-ranging and farmed cervids, with susceptibility governed by various factors, including PrP polymorphisms. While most polymorphisms reduce susceptibility to CWD, there have been no reports of cervid PrP alleles providing absolute resistance to CWD. Studies have focused on understanding the role of animal genetics in predicting, containing, or preventing transmission of CWD in endemic areas.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Bradley A. Maron, Rui-Sheng Wang, Sergei Shevtsov, Stavros G. Drakos, Elena Arons, Omar Wever-Pinzon, Gordon S. Huggins, Andriy O. Samokhin, William M. Oldham, Yasmine Aguib, Magdi H. Yacoub, Ethan J. Rowin, Barry J. Maron, Martin S. Maron, Joseph Loscalzo
Summary: This study analyzed tissue from patients with obstructive hypertrophic cardiomyopathy and heart failure to develop individualized protein-protein interaction networks using RNA-Seq technology. The findings showed that this approach can distinguish between different types of cardiomyopathy and provide key insights into patient-level pathobiology and clinically relevant characteristics of complex diseases.
NATURE COMMUNICATIONS
(2021)
Letter
Cardiac & Cardiovascular Systems
Yasmine Aguib, Mona Allouba, Roddy Walsh, Ayman M. Ibrahim, Sarah Halawa, Alaa Afify, Mohammed Hosny, Pantazis I. Theotokis, Aya Galal, Sara Elshorbagy, Mohamed Roshdy, Heba S. Kassem, Amany Ellithy, Rachel Buchan, Nicola Whiffin, Shehab Anwer, Stuart A. Cook, Ahmed Moustafa, Ahmed ElGuindy, James S. Ware, Paul J. R. Barton, Magdi Yacoub
Review
Cardiac & Cardiovascular Systems
Sarah Halawa, Soni S. Pullamsetti, Charles R. M. Bangham, Kurt R. Stenmark, Peter Dorfmuller, Maria G. Frid, Ghazwan Butrous, Nick W. Morrell, Vinicio A. de Jesus Perez, David I. Stuart, Kevin O'Gallagher, Ajay M. Shah, Yasmine Aguib, Magdi H. Yacoub
Summary: This article discusses the potential causes of COVID-19 heterogeneity and summarizes the pathobiology of the disease, with a focus on the role of the pulmonary vasculature in the acute stage and the potential for developing chronic pulmonary hypertension.
NATURE REVIEWS CARDIOLOGY
(2022)
Review
Virology
Simrika Thapa, Cristobal Marrero Winkens, Waqas Tahir, Maria Arifin, Sabine Gilch, Hermann M. Schatzl
Summary: This article discusses in vitro and in vivo models of chronic wasting disease (CWD) and the impact of gene-editing strategies. Currently, only a limited number of cell lines are suitable for persistent propagation of CWD prions. Gene-editing has proven to be useful for developing CWD models.
Correction
Multidisciplinary Sciences
Bradley A. Maron, Rui-Sheng Wang, Sergei Shevtsov, Stavros G. Drakos, Elena Arons, Omar Wever-Pinzon, Gordon S. Huggins, Andriy O. Samokhin, William M. Oldham, Yasmine Aguib, Magdi H. Yacoub, Ethan J. Rowin, Barry J. Maron, Martin S. Maron, Joseph Loscalzo
NATURE COMMUNICATIONS
(2022)