Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion

Discussion in 'Canada Drug' started by sergdv, 27-Feb-2020.

  1. dmitry001 Well-Known Member

    Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion


    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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    Accordingly, PI4K2A depletion or the overexpression its kinase-dead, dominant negative form leads to the buildup of autophagosomes, inhibits autophagic flux and impairs autophagosome-lysosome fusion. RAB7 positive late endosomes/lysosomes are also enriched with PI4P by PI4K2A. Recent in vitro and in vivo studies revealed that chloroquine affects the endo-lysosomal system and golgi complex thereby modulates autophagic flux through decreasing autophagosome-lysosome fusion. This study invalidated lysosomal degradation function of chloroquine. Chloroquine inhibits lysozyme activity by increasing pH Mizushima et al. 2010. Bafilomycin-A1 is a V-ATPase inhibitor that can block autophagosome–lysosome fusion and prevent lysosome acidification Yamamoto et al. 1998; Klionsky et al. 2008b. A549 and CaLu-1 cells were concurrently treated with GMI and bafilomycin-A1 or chloroquine for 48 h and analysed using the MTT assay.

    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 inhibits autophagic flux by decreasing autophagosome-lysosome fusion

    Prodigiosin impairs autophagosome-lysosome fusion that., Targeting autophagy with small molecules for cancer therapy

  2. Chloroquine and receptor mediated endocytosis
  3. Chloroquine CQ, a 4-aminoquinoline compound, has long been prescribed for the treatment of malaria- 1, autoim mune disorders2 and viral infections 3. It functions primarily by inhibiting lysosomal proteases and blocking autophagosome-lysosome fusion 4. In the range of neutral pH, CQ can freely diffuse across the plasma membrane but

    • Chloroquine inhibits cell growth in human A549 lung cancer..
    • Inhibition of lysosome degradation on autophagosome formation..
    • Inhibition of lysosome degradation on autophagosome..

    What is the best applicable inhibitor of autophagy. that way it inhibits autophagosome-lysosome fusion and degradation. Is this possible and what does this tell us in context of autophagic. Tenovin-6 has attracted significant interest because it activates p53 and inhibits sirtuins. by inhibiting autophagic flux. TP. Autophagosome-lysosome fusion is independent of V-ATPase. Hence, development of specific autophagy modulators that do not perturb general endo-lysosomal traffic possesses unique challenges. In this article, we report a novel small molecule EACC that inhibits autophagic flux by blocking autophagosome–lysosome fusion.

     
  4. votalif User

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  5. Spich User

    Background: The American Academy of Ophthalmology recommendations on screening for chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy are revised in light of new information about the prevalence of toxicity, risk factors, fundus distribution, and effectiveness of screening tools. Chloroquine And Hydroxychloroquine Toxicity - StatPearls. Hydroxychloroquine And Chloroquine Screening 2016 AAO. What can Hydroxychloroquine Plaquenil do to my eyes?
     
  6. dimaonline Moderator

    Yes I'm insane, I stopped taking the plaquenil and boy do I. I am on plaquenil and so fare I have not had sores on my face but I do have them on the bottom of my feet and when they bust open they will have puse like stuff and they of my feet are in bad shape and so for now I'm having to wear my house shose because my regular shose hurt to wear. I all so get these on my back as well and my hands and feet are peeling as well and my Rheumy told me.

    Hydroxychloroquine MedlinePlus Drug Information
     
  7. freshrain Moderator

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