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  • ||||||||||  Neuron specific autophagy-visualizing model in transgenic mice (WCC Halls A-C) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_13782;    
    The GFP/RFP expression ratio in the hippocampus has a tendency of decreasing in both dendrites and cell bodies suggesting the increase of autophagy in these neurons. These results suggest the difference in basal autophagy activity of cellular components and brain regions and expression of GFP-LC3 in neurons of TG mice may reflect the activity of autophagy in vivo.
  • ||||||||||  Defective lysosomal acidification contributes to TNF-TNFR1 mediated neuronal cell death (WCC Halls A-C) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_10119;    
    Importantly, we demonstrate that a novel type of lysosome-targeting acidic nanoparticles restores lysosomal acidification, autophagic activity, and mitochondrial function, as well as rescues neuronal cell death in both cellular models and APP knock-in mouse model of AD. This opens avenues for new therapeutic directions to target lysosomal dysfunction, in addition to the existing efforts in developing receptor-specific inhibitors that target TNFR1 signaling.
  • ||||||||||  The role of LC3-associated phagocytosis in traumatic brain injury mice model (WCC Halls A-C) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_2359;    
    Consistently, in vitro assays using Rubcn deficient bone marrow-derived macrophages (BMDMs) demonstrated that LAP deficiency leads to increased accumulation of myelin debris and lipid droplets within these cells. Together, these findings indicate that LAP participates in phagocytosis and degradation of debris and lipids in macrophages/microglia, thereby contributing to resolve neuroinflammation and promoting recovery after TBI.
  • ||||||||||  A strategy for normalizing TDP-43 proteinopathy by lowering STAU1 abundance with antisense oligonucleotides (ASOs) (WCC 143) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_1690;    
    We have also shown that the autophagy and neurodegenerative disease molecular phenotypes are normalized in C9orf72-BAC(500) transgenic mice, including poly-GA abundance. Targeting STAU1 may be an effective strategy for treating disorders with STAU1 overabundance and TDP-43 proteinopathy characterized with impaired autophagic flux, including amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy (LATE).
  • ||||||||||  sirolimus / Generic mfg.
    Knockdown of NEAT1 prevents post-stroke lipid droplet agglomeration in microglia by regulating autophagy (WCC 207A) -  Nov 3, 2023 - Abstract #Neuroscience2023NEUROSCIENCE_1578;    
    Studying NEAT1-dependent interactions with regard to autophagy and LD agglomeration under hypoxic conditions, the inhibitor and activator of autophagy 3-methyladenine (3-MA) and rapamycin (RAPA) were used, respectively... NEAT1 is a key player of LD agglomeration and autophagy stimulation, and NEAT1 knockdown provides a promising therapeutic value against stroke.
  • ||||||||||  Jakafi (ruxolitinib) / Novartis, Incyte
    TGF (SDCC - Ballroom 20AB) -  Nov 3, 2023 - Abstract #ASH2023ASH_4866;    
    In ongoing work, ROCK inhibitors are further being tested in higher doses alone or in combination with the JAK2 inhibitor ruxolitinib. Overall, our data suggest that TGF
  • ||||||||||  STAT5-Feedback Controls Distinct Metabolic States for Dynamic Transitions between Cellular Activation and Quiescence in Acute Lymphoblastic Leukemia (SDCC - Halls G-H) -  Nov 3, 2023 - Abstract #ASH2023ASH_3932;    
    Our results demonstrate feedback regulators of STAT5, including SOCS2 and CISH are not only biomarkers of increased oncogenic STAT5 activity and a more aggressive course of disease linked to poor overall outcomes. Importantly, negative STAT5 feedback control mechanisms are essential to enable nimble adaptations of B-ALL cells in response to fluctuations of oncogenic signaling strength and availability of nutrients during distinct metabolic states of cellular activation (MYC) and quiescence (BCL6).
  • ||||||||||  Preclinical, Journal:  Semaglutide Pretreatment Induces Cardiac Autophagy to Reduce Myocardial Injury in Septic Mice. (Pubmed Central) -  Nov 1, 2023   
    Taken together, these data indicate that semaglutide provides protection against CLP-triggered myocardial inflammation and injury, potentially by reactivating myocardial autophagy pathways via activation of AMPK signaling. Further mechanistic studies are needed to definitively elucidate the functional significance of AMPK signaling in mediating the beneficial cardiac effects of semaglutide during sepsis.
  • ||||||||||  Review, Journal:  Dissecting the Role of Autophagy-Related Proteins in Cancer Metabolism and Plasticity. (Pubmed Central) -  Oct 31, 2023   
    The importance of metabolic changes, which largely depend on the cancer type and form part of a cancer cell's escape strategy after autophagy modulation, is emphasized. Consequently, pharmacological strategies based on a dual inhibition of metabolic and autophagy pathways emerged and are reviewed critically here.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Mechanism of Paris polyphylla saponin II inducing autophagic to inhibit angiogenesis of cervical cancer. (Pubmed Central) -  Oct 31, 2023   
    Finally, HUVECs were treated with autophagy inhibitors 3-MA, CQ, and PI3K inhibitor LY294002, respectively...In addition, adding autophagy inhibitors can effectively inhibit angiogenesis in cervical cancer. Further research suggests that PPII induces autophagy in HUVEC cells by regulating the PI3K/AKT/mTOR signaling pathway, thereby affecting angiogenesis and inhibiting Hela cell proliferation, lumen formation, invasion, and migration.
  • ||||||||||  hydroxychloroquine / Generic mfg.
    Journal:  Two-Membrane Hybrid Nanobiomimetic Delivery System for Targeted Autophagy Inhibition of Activated Hepatic Stellate Cells To Synergistically Treat Liver Fibrosis. (Pubmed Central) -  Oct 30, 2023   
    Therefore, in this study, a liposome (Lip) and exosome (Exo) two-membrane hybrid nanobiomimetic delivery system HCQ@VA-Lip-Exo was designed, which was modified by vitamin A (VA) to target the aHSCs and carried the autophagy inhibitor hydroxychloroquine (HCQ)...HCQ@VA-Lip-Exo had good aHSC-targeted delivery ability, effective autophagy inhibition, and synergistical anti-liver fibrosis performance, thus reducing the production and deposition of the extracellular matrix to inhibit the liver fibrosis. This combined strategy provided a potential idea for the construction and clinical application of a two-membrane hybrid delivery system as an effective targeted therapy of liver fibrosis.
  • ||||||||||  PD98059 / Wayne State University, SP600125 / BMS
    Journal, PARP Biomarker:  Piperlongumine induces apoptosis via the MAPK pathway and ERK?mediated autophagy in human melanoma cells. (Pubmed Central) -  Oct 30, 2023   
    Pretreatment of A375P cells with the ERK inhibitor PD98059 and the JNK inhibitor SP600125 followed by treatment with PL confirmed that apoptosis and autophagy were mediated via the MAPK/ERK pathway by western blot. In summary, the present study provided empirical evidence supporting the anticancer effects of PL on human melanoma cells and indicated the potential of PL as a treatment for melanoma.
  • ||||||||||  chloroquine phosphate / Generic mfg.
    Journal:  Shikonin promotes hypertrophic scar repair by autophagy of hypertrophic scar-derived fibroblasts. (Pubmed Central) -  Oct 29, 2023   
    Therefore, UCNPs@FL-MEL might be an important reference for the design and development of future nanotherapeutic agents. These findings suggested that SHI promoted autophagy of HSFs cells, and the potential mechanism may be related to the AMPK/mTOR signal pathway, which provided new insights for the treatment of hypertrophic scars.
  • ||||||||||  sirolimus / Generic mfg.
    Journal:  Loss of SARM1 ameliorates secondary thalamic neurodegeneration after cerebral infarction. (Pubmed Central) -  Oct 29, 2023   
    Taken together, SARM1 contributes to secondary thalamic neurodegeneration after cerebral infarction, at least partly through autophagy inhibition. SARM1 deficiency is a potential therapeutic strategy for secondary thalamic neurodegeneration and functional deficits after stroke.
  • ||||||||||  Journal:  High-density lipoprotein regulates angiogenesis by affecting autophagy via miRNA-181a-5p. (Pubmed Central) -  Oct 29, 2023   
    In contrast, dHDL inhibited angiogenesis, at least partially, by increasing miR-181a-5p expression, which decreased autophagy and eNOS expression, resulting in a decrease in NO production and an increase in O generation. Our findings reveal a novel mechanism by which HDL affects angiogenesis by regulating autophagy and provide a therapeutic target for dHDL-impaired angiogenesis.
  • ||||||||||  Role of IRE1 and Autophagy in the Profibrotic Mechanism of Graves Orbitopathy (POSTER THEATER) -  Oct 28, 2023 - Abstract #AAO2023AAO_1818;    
    Similarly, bafilomycin A1, a late-phase autophagy inhibitor, decreased the expression of profibrotic proteins. Conclusion IRE1 mediates autophagy process and profibrotic mechanism in GO, suggesting more comprehensive interpretation of GO pathogenesis.
  • ||||||||||  Journal:  Novel Potent Autophagy Inhibitor Ka-003 Inhibits Dengue Virus Replication. (Pubmed Central) -  Oct 28, 2023   
    Taken together, data indicate that Ka-003 hampered autophagy and limited DENV replication. The low cytotoxicity of Ka-003 suggests its therapeutic potential, which warrants further studies for the lead optimization of the compound for dengue treatment.
  • ||||||||||  MG132 / Jilin University, Dorothy M. Davis Heart and Lung Research Institute
    Journal:  Activation of Chaperone-Mediated Autophagy Inhibits the Aryl Hydrocarbon Receptor Function by Degrading This Receptor in Human Lung Epithelial Carcinoma A549 Cells. (Pubmed Central) -  Oct 28, 2023   
    We have observed that the AHR protein levels increase in the presence of chloroquine (CQ), an autophagy inhibitor, in a dose-dependent manner...This decrease suppresses the ligand-dependent activation of the AHR target gene transcription, and can be reversed by CQ but not MG132...Suppression of the epithelial-to-mesenchymal transition in A549 cells is observed when the AHR gene is knocked out or the AHR protein level is reduced by 6-AN. Collectively, we have provided evidence supporting that AHR is continuously undergoing CMA and activation of CMA suppresses the AHR function in A549 cells.
  • ||||||||||  Erleada (apalutamide) / J&J
    Review, Journal, Combination therapy:  Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer. (Pubmed Central) -  Oct 28, 2023   
    Unlike most of our previous reports, where multiple functional forms of autophagy were identified, making it difficult if not impossible to propose autophagy inhibition as a therapeutic strategy, the cytoprotective form of autophagy appears to predominate in the case of androgen deprivation therapies. This opens a potential pathway for improving the outcomes for prostate cancer patients once effective and reliable pharmacological autophagy inhibitors have been developed.
  • ||||||||||  Preclinical, Journal:  Streptococcal Arginine Deiminase Inhibits T Lymphocyte Differentiation In Vitro. (Pubmed Central) -  Oct 28, 2023   
    One of the prominent ADI effects was the inhibition of autophagy processes in CD8+ CM and EM as well as CD4+ CM, EM, and TEMRA T cell subsets. The data obtained confirm arginine's crucial role in controlling immune reactions and suggest that streptococcal ADI may downregulate adaptive immunity and immunological memory.
  • ||||||||||  Journal:  Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy. (Pubmed Central) -  Oct 24, 2023   
    Pharmacological inhibition or genetic depletion of ACSS2 in the streptozotocin-induced diabetic mouse model greatly ameliorated kidney injury and podocyte dysfunction. To conclude, ACSS2 activation promoted podocyte injury in DN by raptor/mTORC1-mediated autophagy inhibition.
  • ||||||||||  galidesivir (BCX4430) / BioCryst
    Preclinical, Journal:  BCX4430 inhibits the replication of rabies virus by suppressing mTOR-dependent autophagy invitro. (Pubmed Central) -  Oct 23, 2023   
    Furthermore, BCX4430 dose- and time-dependently inhibited RABV replication via mTOR-dependent autophagy inhibition in N2a cells with increased phospho-mTOR and phospho-SQSTM1 and decreased LC3-II levels. Taken together, these findings suggest that BCX4430 has potent anti-RABV activity in vitro and might provide a basis for the development of novel drug therapies against RABV.