title: Discovery and characterization of a mammalian amyloid disaggregation activity.
abstract: The formation of amyloid, a cross-beta-sheet fibrillar aggregate, is associated with a variety of aging-associated degenerative diseases. Herein, we report the existence of a mammalian amyloid disaggregase activity that is present in all tissues and cell types tested. Homogenates from mammalian tissues and cell lines are able to disaggregate amyloid fibrils composed of amyloid beta (A beta)(1-40) or the 8 kDa plasma gelsolin fragment. The mammalian disaggregase activity is sensitive to proteinase K digestion and can be uncoupled from proteolysis activity using a protease inhibitor cocktail. Amyloid disaggregation and proteolysis activities are remarkably resistant to changes in temperature and pH. Identification and manipulation of the proteins responsible for the amyloid disaggregation/degradation activities offers the possibility of ameliorating aggregation-associated diseases.
authors.affiliation: Department of Chemistry, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: Amber N
authors.initials: AN
authors.lastname: Murray
authors.forename: James P
authors.initials: JP
authors.lastname: Solomon
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Wang
authors.forename: William E
authors.initials: WE
authors.lastname: Balch
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D058255:Protease Nexins; D055503:Protein Multimerization; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D013696:Temperature
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface