title: Huntington's disease: underlying molecular mechanisms and emerging concepts.
abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder for which no disease modifying treatments exist. Many molecular changes and cellular consequences that underlie HD are observed in other neurological disorders, suggesting that common pathological mechanisms and pathways may exist. Recent findings have enhanced our understanding of the way cells regulate and respond to expanded polyglutamine proteins such as mutant huntingtin. These studies demonstrate that in addition to effects on folding, aggregation, and clearance pathways, a general transcriptional mechanism also dictates the expression of polyglutamine proteins. Here, we summarize the key pathways and networks that are important in HD in the context of recent therapeutic advances and highlight how their interplay may be of relevance to other protein folding disorders.
authors.affiliation: Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208, USA.
authors.forename: John
authors.initials: J
authors.lastname: Labbadia
authors.forename: Richard I
authors.initials: RI
authors.lastname: Morimoto
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding; D055550:Protein Stability; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D010455:Peptides; C097188:polyglutamine; D046988:Proteasome Endopeptidase Complex
keywords: Huntington's disease; molecular mechanisms; therapeutic approaches