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Clearance of Mutant Aggregate-Prone Proteins by Autophagy

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The accumulation of mutant aggregate-prone proteins is a feature of several human disorders, collectively referred to as protein conformation disorders or proteinopathies. We have shown that autophagy, a cytosolic, non-specific bulk degradation system, is an important clearance route for many cytosolic toxic, aggregate-prone proteins, like mutant huntingtin and mutant -synucleins. Induction of autophagy enhances the clearance of both soluble and aggregated forms of the mutant protein, and protects against toxicity caused by these mutations in cell, fly, and mouse models. Inhibition of autophagy has opposite effects. Thus, the autophagic pathway may represent a possible therapeutic target in the treatment of certain protein conformation disorders.
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