title: Autophagy in Huntington disease and huntingtin in autophagy.
abstract: Autophagy is an important biological process that is essential for the removal of damaged organelles and toxic or aggregated proteins by delivering them to the lysosome for degradation. Consequently, autophagy has become a primary target for the treatment of neurodegenerative diseases that involve aggregating proteins. In Huntington disease (HD), an expansion of the polyglutamine (polyQ) tract in the N-terminus of the huntingtin (HTT) protein leads to protein aggregation. However, HD is unique among the neurodegenerative proteinopathies in that autophagy is not only dysfunctional but wild type (wt) HTT also appears to play several roles in regulating the dynamics of autophagy. Herein, we attempt to integrate the recently described novel roles of wtHTT and altered autophagy in HD.
authors.affiliation: Centre for Molecular Medicine and Therapeutics (CMMT), Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: dalem@cmmt.ubc.ca.
authors.forename: Dale D O
authors.initials: DD
authors.lastname: Martin
authors.affiliation: Centre for Molecular Medicine and Therapeutics (CMMT), Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Safia
authors.initials: S
authors.lastname: Ladha
authors.affiliation: Centre for Molecular Medicine and Therapeutics (CMMT), Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Dagmar E
authors.initials: DE
authors.lastname: Ehrnhoefer
authors.affiliation: Centre for Molecular Medicine and Therapeutics (CMMT), Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. Electronic address: mrh@cmmt.ubc.ca.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hayden
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: Huntington disease; autophagy; caspases; myristoylation; neurodegeneration; post-translational modifications; therapies; trafficking