title: Clearance of mutant aggregate-prone proteins by autophagy.
abstract: 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 alpha-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.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Brinda
authors.initials: B
authors.lastname: Ravikumar
authors.forename: Sovan
authors.initials: S
authors.lastname: Sarkar
authors.forename: David C
authors.initials: DC
authors.lastname: Rubinsztein
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004591:Electrophoresis, Polyacrylamide Gel; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000378:metabolism; D007150:Immunohistochemistry; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051843:Synucleins / Q000235:genetics / Q000378:metabolism
chemical_list: C499524:Htt protein, rat; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051843:Synucleins