Julia Corral Sarasa’s Post

📃Scientific paper: LYECs: lysosome-enhancing compounds as potential therapeutic approaches for Alzheimer disease Abstract: More than 55 million people are suffering from Alzheimer's disease (AD), but there is still no effective treatment for it. Therefore, novel therapeutic approaches and regulatory mechanisms of protein quality control need to be further evaluated and dissected. The lysosome is one of the major degradative organelles that maintain cellular homeostasis and protein quality control. In our recent study, we have identified a group of LYsosome-Enhancing Compounds (LYECs), which significantly promote the activation of TFEB (transcription factor EB) and lysosome biogenesis via inhibiting dopamine transporters (DAT). Injection of LH2-051, a member of the LYECs identified in this study, significantly improves learning, memory, and cognitive function of APP-PSEN1 mice, in which the enhanced capability of lysosomal degradation promotes the clearance of amyloid protein aggregates. In summary, this study reports novel mechanisms of neurotransporter-mediated lysosome biogenesis and shows that DAT inhibition can alleviate the pathogenesis of Alzheimer's disease. Continued on ES/IODE ➡️ https://etcse.fr/d0a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health

📃Scientific paper: LYECs: lysosome-enhancing compounds as potential therapeutic approaches for Alzheimer disease Abstract: More than 55 million people are suffering from Alzheimer's disease (AD), but there is still no effective treatment for it. Therefore, novel therapeutic approaches and regulatory mechanisms of protein quality control need to be further evaluated and dissected. The lysosome is one of the major degradative organelles that maintain cellular homeostasis and protein quality control. In our recent study, we have identified a group of LYsosome-Enhancing Compounds (LYECs), which significantly promote the activation of TFEB (transcription factor EB) and lysosome biogenesis via inhibiting dopamine transporters (DAT). Injection of LH2-051, a member of the LYECs identified in this study, significantly improves learning, memory, and cognitive function of APP-PSEN1 mice, in which the enhanced capability of lysosomal degradation promotes the clearance of amyloid protein aggregates. In summary, this study reports novel mechanisms of neurotransporter-mediated lysosome biogenesis and shows that DAT inhibition can alleviate the pathogenesis of Alzheimer's disease. Continued on ES/IODE ➡️ https://etcse.fr/d0a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health

Breakthrough in Liver Disease Research! I am honored to share that our latest research, published in Science Translational Medicine has uncovered a potential cure for Nonalcoholic Steatohepatitis (NASH), a severe liver disease affecting millions globally. We identified the pivotal role of the protein Hypoxia-Inducible Factor 2-alpha (HIF-2α) in driving liver inflammation and damage in NASH. By inhibiting HIF-2α, we demonstrated that liver damage could be reduced, offering new hope for those battling this disease. This discovery could transform the way NASH is treated, paving the way for innovative therapies and providing relief to millions of patients, including in my home region of Kashmir, where the prevalence of NASH is rising rapidly due to lifestyle changes. I hope this achievement serves as a reminder to young scientists, especially from underrepresented regions, that no dream is too big and no goal is too far. With dedication, we can overcome barriers and make meaningful contributions to the world. https://bit.ly/4gFnRk6 #ScientificBreakthrough #Research #Science #LiverDisease #Healthcare #NASH #MedicalResearch #Kashmir #UCSD #STEM #PhD #Metabolism #Discovery UC San Diego UC San Diego Health UC San Diego School of Medicine University University

New Research from Ralph J DeBerardinis' Lab Uncovers the role of HGRPT in Mitochondrial Disease A new study published by Wu et al in Cell Metabolism uncovers a link between mitochondrial dysfunction and purine metabolism, a finding that could have implications for patients affected by mitochondrial disorders. The research reveals that impaired mitochondrial function alters the way cells produce purines, the building blocks of DNA and RNA. This shift makes the salvage enzyme HGPRT essential for cellular growth when mitochondrial respiration is compromised. Key Findings: Altered Purine Metabolism: Mitochondrial dysfunction leads to a common perturbation in purine metabolism, observed in both patient cells and cell models with induced mitochondrial defects. Suppression of de novo Purine Synthesis: Impaired mitochondrial function suppresses the de novo purine synthesis pathway, forcing cells to rely on the salvage pathway to maintain purine pools. Importance of HGPRT: The salvage enzyme HGPRT becomes crucial for cell growth under mitochondrial dysfunction. Does identifying the dependence of cells on purine salvage under these conditions open up new avenues for therapeutic intervention in mitochondrial disorders? Read the full research article in Cell Metabolism: https://lnkd.in/eZwDb5HE

Glad to share our new work that made to the cover of the April 10th issue of #ScienceTranslationalMedicine. Some patients with #RheumatoidArthritis (#RA) don’t benefit from any of the available anti-inflammatory therapies. With a #graph based #MachineLearning method, we identified a group of genes, expressed by joint lining fibroblasts, enriched for neuronal growth pathways, and predicted to interact with sensory nerves. We saw sensory nerves accompanying blood vessels growing towards the lining layer, placing the cells that most robustly express #pain associated genes adjacent to sensory nerves, and found that #RA synovial fibroblasts augment growth of sensory nerves in vitro. We hope our study can shed light on alternative #pain mechanisms for #RA patients other than #inflammation, and trigger more targeted treatment strategies. Truly a comprehensive team effort. Thanks for the leadership from the amazing Dana Orange, the persistence and passion from the brilliant Zilong Bai, the expertise and insights from Caryn Hale, Fan Zhang, PhD, Robert Darnell, and many others. Also appreciate the help from Weill Cornell Medicine #PBSB PhD students Nicholas Bartelo and Haotan Zhang during their rotations at my lab. Paper link: https://lnkd.in/esDJ4EeJ #RheumatoidArthritis #RA #MachineLearning #Pain #DrugDevelopment

𝐄𝐱𝐜𝐢𝐭𝐢𝐧𝐠 𝐃𝐢𝐬𝐜𝐨𝐯𝐞𝐫𝐲 𝐢𝐧 𝐋𝐢𝐯𝐞𝐫 𝐃𝐢𝐬𝐞𝐚𝐬𝐞 𝐑𝐞𝐬𝐞𝐚𝐫𝐜𝐡! We are thrilled to share groundbreaking findings on the role of  𝐒𝐞𝐦𝐚𝐩𝐡𝐨𝐫𝐢𝐧-𝟑𝐀 𝐢𝐧 𝐥𝐢𝐯𝐞𝐫 𝐝𝐢𝐬𝐞𝐚𝐬𝐞, recently published in *Nature Cardiovascular Research*. The study highlights how elevated Sema3a impacts liver sinusoidal endothelial cells, contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). 𝐏𝐚𝐦𝐆𝐞𝐧𝐞'𝐬 𝐤𝐢𝐧𝐚𝐬𝐞 𝐚𝐜𝐭𝐢𝐯𝐢𝐭𝐲 𝐩𝐫𝐨𝐟𝐢𝐥𝐢𝐧𝐠 played a crucial role in this research, identifying key signaling pathways. This innovative technology is paving the way for targeted therapies, offering hope for reversing or preventing MASLD progression. Congratulations to the dedicated researchers for this significant achievement! Daniel Eberhard Sydney Balkenhol Eckhard Lammert 𝐑𝐞𝐚𝐝 𝐦𝐨𝐫𝐞: 𝐍𝐚𝐭𝐮𝐫𝐞 𝐀𝐫𝐭𝐢𝐜𝐥𝐞 (https://lnkd.in/exs_MEvz) #LiverResearch #KinaseActivityProfiling #KinomePro #PamGene #MASLD #Biotechnology #HealthInnovation University of Düsseldorf, Faculty of Mathematics and Natural Sciences

Paper alert! Our recent study on the quantification of amyloid-β peptides by LC-MS/MS in CAA, AD-like and control subjects has recently been published in the Journal of Neurochemistry. Discover more in the Radboudumc Research news item below, and read the full text!

📃Scientific paper: LYECs: lysosome-enhancing compounds as potential therapeutic approaches for Alzheimer disease Abstract: More than 55 million people are suffering from Alzheimer's disease (AD), but there is still no effective treatment for it. Therefore, novel therapeutic approaches and regulatory mechanisms of protein quality control need to be further evaluated and dissected. The lysosome is one of the major degradative organelles that maintain cellular homeostasis and protein quality control. In our recent study, we have identified a group of LYsosome-Enhancing Compounds (LYECs), which significantly promote the activation of TFEB (transcription factor EB) and lysosome biogenesis via inhibiting dopamine transporters (DAT). Injection of LH2-051, a member of the LYECs identified in this study, significantly improves learning, memory, and cognitive function of APP-PSEN1 mice, in which the enhanced capability of lysosomal degradation promotes the clearance of amyloid protein aggregates. In summary, this study reports novel mechanisms of neurotransporter-mediated lysosome biogenesis and shows that DAT inhibition can alleviate the pathogenesis of Alzheimer's disease. Continued on ES/IODE ➡️ https://etcse.fr/d0a ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you. #alzheimer #science #health

🌟New Study Reveals Key Determinant in Liver Disease! 🌍Non-alcoholic fatty liver disease (NAFLD) affects a third of the global population, leading to #LiverFibrosis, which significantly impacts disease severity and mortality. A recent study has now identified a crucial factor contributing to this condition. Researchers from Novartis (Novartis Biomedical Research, Basel) have used #CRISPR and #SpatialTranscriptomics technologies on primary human hepatic stellate cells to pinpoint ZNF469 as a key regulator of collagen expression, crucial for #LiverFibrosis in #NAFLD. This discovery was made through a comprehensive analysis involving transcriptional profiling of 108 human liver biopsies, covering the entire spectrum of #NAFLD. The #preprint study highlights how #ZNF469 directly interacts with genes and regulatory elements to control collagen levels and matrix homeostasis, marking it as a critical target for potential therapies. 💡 This breakthrough provides hope for better understanding and treating NAFLD-associated liver fibrosis, potentially saving millions of lives. 📖 Read the pre-print: https://hubs.ly/Q02vkkWS0 #Vizgen #MERSCOPE #LiverDisease

"The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that is widely expressed in epithelial cells of the lung, intestine, pancreas, and reproductive tract, where it regulates salt and fluid homeostasis. Mutations that disrupt CFTR biosynthesis, folding, trafficking, or ion permeation cause #CysticFibrosis (CF), a lethal genetic disease with no cure! In addition, acquired CFTR dysfunction—through smoking, for example—plays an important role in the initiation and progression of chronic obstructive pulmonary disease (#COPD). On the other hand, excessive activation of CFTR by bacterial pathogens such as Vibrio cholerae and enterotoxigenic Escherichia coli leads to secretory #Diarrhea, a major cause of mortality in children under the age of five. Hyperactivity of CFTR is also a key driver in the pathogenesis of autosomal dominant polycystic kidney disease (#ADPKD)! #SmallMolecules that improve CFTR folding (correctors) or function (potentiators) are clinically available. However, the only potentiator, #Ivacaftor, has suboptimal pharmacokinetics and inhibitors have yet to be clinically developed!" Do not miss this amazing open-access article published in Cell Press last month, in which researchers from The Rockefeller University, University of California, San Francisco, Taras Shevchenko National University of Kyiv and Universität Erlangen-Nürnberg combine #MolecularDocking, #Electrophysiology, #CryoEM, and #MedicinalChemistry to identify CFTR modulators: https://lnkd.in/gsDSEk8S After docking ∼155 million molecules into the potentiator site on CFTR, the groups synthesized 53 test ligands, and used structure-based optimization to identify novel candidate modulators. This approach uncovered mid-nanomolar potentiators, as well as #Inhibitors, that bind to the same #Allosteric site. These molecules represent potential leads for #DrugDevelopment of more effective compounds for cystic fibrosis and secretory diarrhea, demonstrating the feasibility of large-scale docking for ion channel #DrugDiscovery!