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FEBS J. 2008 Sep;275(17):4263-70. doi: 10.1111/j.1742-4658.2008.06562.x. Epub 2008 Jul 15.

Huntington's disease: degradation of mutant huntingtin by autophagy.

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Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Addenbrooke's Hospital, UK.


Autophagy is a nonspecific bulk degradation pathway for long-lived cytoplasmic proteins, protein complexes, or damaged organelles. This process is also a major degradation pathway for many aggregate-prone, disease-causing proteins associated with neurodegenerative disorders, such as mutant huntingtin in Huntington's disease. In this review, we discuss factors regulating the degradation of mutant huntingtin by autophagy. We also report the growing list of new drugs/pathways that upregulate autophagy to enhance the clearance of this mutant protein, as autophagy upregulation may be a tractable strategy for the treatment of Huntington's disease.

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