title: The small heat shock proteins αB-crystallin and Hsp27 suppress SOD1 aggregation in vitro.
abstract: Amyotrophic lateral sclerosis is a devastating neurodegenerative disease. The mechanism that underlies amyotrophic lateral sclerosis (ALS) pathology remains unclear, but protein inclusions are associated with all forms of the disease. Apart from pathogenic proteins, such as TDP-43 and SOD1, other proteins are associated with ALS inclusions including small heat shock proteins. However, whether small heat shock proteins have a direct effect on SOD1 aggregation remains unknown. In this study, we have examined the ability of small heat shock proteins αB-crystallin and Hsp27 to inhibit the aggregation of SOD1 in vitro. We show that these chaperone proteins suppress the increase in thioflavin T fluorescence associated with SOD1 aggregation, primarily through inhibiting aggregate growth, not the lag phase in which nuclei are formed. αB-crystallin forms high molecular mass complexes with SOD1 and binds directly to SOD1 aggregates. Our data are consistent with an overload of proteostasis systems being associated with pathology in ALS.
authors.affiliation: Illawarra Health and Medical Research Institute, School of Biological Sciences, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia. jyerbury@uow.edu.au
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Yerbury
authors.forename: Dane
authors.initials: D
authors.lastname: Gower
authors.forename: Laura
authors.initials: L
authors.lastname: Vanags
authors.forename: Kate
authors.initials: K
authors.lastname: Roberts
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Lee
authors.forename: Heath
authors.initials: H
authors.lastname: Ecroyd
mesh_terms: D019943:Amino Acid Substitution; D052160:Benzothiazoles; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D055551:HSP27 Heat-Shock Proteins; C000606290:SOD1 protein, human; D013844:Thiazoles; D038203:alpha-Crystallin B Chain; C009462:thioflavin T; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1