Nat Commun: Autophagy-activated drugs can remove Alzheimer's-related tau protein seofs long-term
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Last Update: 2020-07-14
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Source: Internet
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Author: User
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Tau protein pathology is a neurodegenerative disease associated with the accumulation of abnormal tau protein in the brainIn vitro, patient iPSC-derived neuronal cell models replicate disease-related phenotypes that can be targeted for drug discoveryrecently, researchers explored autophagy as a mechanism to reduce the burden of human neurons and found mTOR inhibitors OSI-027, AZD2014, and AZD8055 in small molecular screeningThese compounds are more effective than rapamycin and strongly reduce phosphorylation and insoluble tau, thereby reducing tau-mediated neuronal stress vulnerabilitymTORC1 inhibition and autophagy activity are directly related to tau removalIt is important to note that single-dose treatment reduces tau levels and toxicity by 12 days, reflecting the continuing effects on mTORC1 inhibition and autophagythis new insight into the efficacy of mTOR inhibitors regulating neuronal autophagy may help develop treatments for tau-related diseases
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