title: Protein aggregation and ER stress.
abstract: Protein aggregation is a common feature of the protein misfolding or conformational diseases, among them most of the neurodegenerative diseases. These disorders are a major scourge, with scarce if any effective therapies at present. Recent research has identified ER stress as a major mechanism implicated in cytotoxicity in these diseases. Whether amyloid-β or tau in Alzheimer's, α-synuclein in Parkinson's, huntingtin in Huntington's disease or other aggregation-prone proteins in many other neurodegenerative diseases, there is a shared pathway of oligomerization and aggregation into amyloid fibrils. There is increasing evidence in recent years that the toxic species, and those that evoke ER stress, are the intermediate oligomeric forms and not the final amyloid aggregates. This review focuses on recent findings on the mechanisms and importance of the development of ER stress upon protein aggregation, especially in neurodegenerative diseases, and possible therapeutic approaches that are being examined. This article is part of a Special Issue entitled SI:ER stress.
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Navit
authors.initials: N
authors.lastname: Ogen-Shtern
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Tamuz
authors.initials: T
authors.lastname: Ben David
authors.affiliation: Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel; Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: gerardo@post.tau.ac.il.
authors.forename: Gerardo Z
authors.initials: GZ
authors.lastname: Lederkremer
mesh_terms: D000818:Animals; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology*; D066263:Protein Aggregation, Pathological / Q000209:etiology*; D017510:Protein Folding
keywords: Alzheimer's disease; Huntington's disease; Neurodegenerative disease; Parkinson's disease; Protein misfolding; Unfolded protein response