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- W2583700773 endingPage "a024612" @default.
- W2583700773 startingPage "a024612" @default.
- W2583700773 abstract "Normal tau homeostasis is achieved when the synthesis, processing, and degradation of the protein is balanced. Together, the pathways that regulate tau homeostasis ensure that the protein is at the proper levels and that its posttranslational modifications and subcellular localization are appropriately controlled. These pathways include the enzymes responsible for posttranslational modifications, those systems that regulate mRNA splicing, and the molecular chaperones that control tau turnover and its binding to microtubules. In tauopathies, this delicate balance is disturbed. Tau becomes abnormally modified by posttranslational modification, it loses affinity for microtubules, and it accumulates in proteotoxic aggregates. How and why does this imbalance occur? In this review, we discuss how molecular chaperones and other components of the protein homeostasis (e.g., proteostasis) network normally govern tau quality control. We also discuss how aging might reduce the capacity of these systems and how tau mutations might further affect this balance. Finally, we discuss how small-molecule inhibitors are being used to probe and perturb the tau quality-control systems, playing a particularly prominent role in revealing the logic of tau homeostasis. As such, there is now interest in developing these chemical probes into therapeutics, with the goal of restoring normal tau homeostasis to treat disease." @default.
- W2583700773 created "2017-02-10" @default.
- W2583700773 creator A5043300541 @default.
- W2583700773 creator A5067529915 @default.
- W2583700773 creator A5074964983 @default.
- W2583700773 date "2017-02-03" @default.
- W2583700773 modified "2023-09-30" @default.
- W2583700773 title "Therapeutic Strategies for Restoring Tau Homeostasis" @default.
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