Chloroquine autophagy mechanism

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  1. Stass287 Well-Known Member

    Chloroquine autophagy mechanism


    Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms.

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    Inhibition of autophagy using chloroquine or hydroxychloroquine has already shown promise in clinical trials and numerous other clinical trials are ongoing to determine the optimal tumors to treat. Autophagy is a self-digesting mechanism responsible for removal of damaged organelles, malformed proteins during biosynthesis, and nonfunctional long-lived proteins by lysosome. Autophagy has been divided into three general types depending on the mechanism by which intracellular materials are delivered into lysosome for degradation that is, microautophagy, chaperone-mediated autophagy CMA. Aug 27, 2018 Up until recently, inhibitory effects of chloroquine on the late stage of autophagy was thought to be the major mechanism underlying cancer cells death from chloroquine. However, recent research provided compelling evidence that autophagy-inhibiting activities of chloroquine are dispensable for its ability to suppress tumor cells growth.

    To address this, we cultured primary rat cortical neurons from E18 embryos and used the Seahorse XF96 analyzer and a targeted metabolomics approach to measure the effects of bafilomycin A1 and chloroquine on bioenergetics and metabolism. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics.

    Chloroquine autophagy mechanism

    Chloroquine Targets Pancreatic Cancer Stem Cells via., Autophagy Mechanism, Regulation, Functions, and Disorders

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  5. Nov 15, 2015 Chloroquine is commonly used to study the role of endosomal acidification in cellular processes 2, 3, such as the signaling of intracellular TLRs. Moreover, Chloroquine inhibits autophagy as it raises the lysosomal pH, which leads to inhibition of both fusion of autophagosome with lysosome and lysosomal protein degradation 4.

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    Autophagy is a homeostatic cellular recycling system that is responsible for degrading damaged or unnecessary cellular organelles and proteins. Cancer cells are thought to use autophagy as a source of energy in the unfavorable metastatic environment, and a number of clinical trials are now revealing the promising role of chloroquine, an autophagy inhibitor, as a novel antitumor drug. On the. Hydroxychloroquine and chloroquine are antimalarial drugs commonly used for the treatment of rheumatic diseases. Multiple mechanisms might explain the efficacy and adverse effects of these drugs. Tumor cells require autophagy to remove misfolded proteins or damaged cellular organelles. SBI-0206965 was shown to suppress autophagy induced by mTOR inhibition. mTOR signaling is often hyperactive in many tumors and can drive proliferation, so mTOR inhibitors are being investigated as anticancer agents.

     
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