title: Endoplasmic reticulum stress: The cause and solution to Huntington's disease?
abstract: Accumulation of misfolded proteins is a hallmark of many human diseases, including several incurable neurological disorders, such as Huntington's disease (HD). In HD, expansion of a polyglutamine stretch within the first exon of the Huntingtin protein (Htt) leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Several studies in various organisms (from yeast to humans) have identified the accumulation of misfolded secretory proteins in the endoplasmic reticulum (ER stress) as a crucial determinant of cellular toxicity in HD. In this review, we highlight the recent research linking HD to ER stress. We also discuss how the modulation of signaling pathways responsible for coping with misfolded protein accumulation in the ER may constitute attractive methods to reduce toxicity and identify new therapeutic targets for treatment of HD. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Canada N6A 5C1.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Canada N6A 5C1.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Chadwick
authors.affiliation: Department of Anatomy and Cell Biology, The University of Western Ontario, London, Canada N6A 5C1. Electronic address: plajoie3@uwo.ca.
authors.forename: Patrick
authors.initials: P
authors.lastname: Lajoie
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics / Q000378:metabolism; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein
keywords: Cell signaling; ER stress; Huntington's disease; Neurodegeneration; Unfolded protein response