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. 2021 Jun 22;15:2747–2767. doi: 10.2147/DDDT.S308973

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© 2021 Huang et al.

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Mechanism of the autophagy regulating effect of the antiparasitic agents. The autophagy-promotive agents are shown in purple boxes and autophagy-inhibitory agents are shown in red boxes. mTOR is one of the major inhibitory elements that targets the initiation of the autophagic procedure. SM1044, DHA and ivermectin inhibit mTOR and subsequently activate the autophagic process. Flubendazole disassociates mTOR from the lysosome, leading to nuclear translocation of TFEB and finally upregulates LC3. It can also phosphorylate Bcl-2 via JNK-1 activation and release its inhibition on Beclin-1, which is part of the Class III PI3K complex. Flubendazole also binds with EVA1A and further induces EVA1A mediated autophagy. HCQ, DC661 and Lys05 inhibit the PPT1 and result in accumulation of palmitoylated proteins, which would concurrently inhibit lysosome and mTOR. Nitazoxanide and CQ/HCQ inhibit the fusion between autophagosome and lysosome. Mefloquine targets RAB5/7 and LAMP1/2 to inhibit the lysosome maturation.