title: Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS.
abstract: A dominant mutation in the gene for copper-zinc superoxide dismutase (SOD1) is the most frequent cause of the inherited form of amyotrophic lateral sclerosis. Mutant SOD1 provokes progressive degeneration of motor neurons by an unidentified acquired toxicity. Exploiting both affinity purification and mass spectrometry, we identified a novel interaction between heat-shock protein 105 (Hsp105) and mutant SOD1. We detected this interaction both in spinal cord extracts of mutant SOD1(G93A) transgenic mice and in cultured neuroblastoma cells. Expression of Hsp105, which is found in mouse motor neurons, was depressed in the spinal cords of SOD1(G93A) mice as disease progressed, while levels of expression of two other heat-shock proteins, Hsp70 and Hsp27, were elevated. Moreover, Hsp105 suppressed the formation of mutant SOD1-containing aggregates in cultured cells. These results suggest that techniques that raise levels of Hsp105 might be promising tools for alleviation of the mutant SOD1 toxicity.
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamashita
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawamata
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Kanki
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakamizo
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Hatayama
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Kyoto University Graduate School of Medicine, Kyoto, JapanYamanaka Research Unit, RIKEN Brain Science Institute, Wako, JapanHorizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Kyoto, JapanDepartment of Biochemistry, Kyoto Pharmaceutical University, Kyoto, JapanDepartment of Neurology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Shimohama
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism; D009154:Mutation / Q000502:physiology*; D009447:Neuroblastoma; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D050957:HSP110 Heat-Shock Proteins; C490783:Hsp105 protein, mouse; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase