Clearance of mutant proteins as a therapeutic target in neurodegenerative diseases.
Accumulation and aggregation of disease-causing proteins is a hallmark of several neurodegenerative disorders such as Parkinson, Alzheimer, and Huntington diseases. One of the main goals of research in neurodegenerative disorders has been to improve clearance of these accumulated proteins. Using the example of Huntington disease, I discuss strategies to selectively activate cellular degradation machinery to improve clearance of the mutant protein and to identify therapeutic targets for the treatment of Huntington disease and related neurodegenerative disorders.
Krainc
Dimitri
D
Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, 114 16th St, Room 2007, Charlestown, MA 02129, USA. dkrainc@partners.org
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
C086055:HTT protein, human; D056572:Histone Deacetylase Inhibitors; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins