Clearance of Mutant Aggregate-Prone Proteins by Autophagy

  • Brinda Ravikumar
  • Sovan Sarkar
  • David C. Rubinsztein
Part of the Methods in Molecular Biology™ book series (MIMB, volume 445)


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 \({\bf \alpha}\)-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.

Key Words

Autophagy aggregate-prone proteins Huntington’s disease rapamycin 



We thank T. Yoshimori (National Institute of Genetics, Japan) for EGFP-LC3 construct. We are grateful to the Wellcome Trust (Senior Clinical Fellowship to DCR), MRC, EU (EUROSCA) and Muscular Dystrophy Campaign for funding.


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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Brinda Ravikumar
    • 1
    • 2
  • Sovan Sarkar
    • 1
    • 2
  • David C. Rubinsztein
    • 1
    • 2
  1. 1.Department of Medical GeneticsUniversity of CambridgeCambridgeUK
  2. 2.Cambridge Institute for Medical ResearchAddenbrooke′s HospitalCambridgeUK

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