Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis

被引:52
|
作者
Tokuda, Eiichi [1 ]
Takei, Yo-ichi [2 ]
Ohara, Shinji [2 ,3 ]
Fujiwara, Noriko [4 ]
Hozumi, Isao [5 ,6 ]
Furukawa, Yoshiaki [1 ]
机构
[1] Keio Univ, Dept Chem, Lab Mechanist Chem Biomol, Yokohama, Kanagawa 2238522, Japan
[2] Matsumoto Med Ctr, Dept Neurol, Matsumoto, Nagano 3990021, Japan
[3] Iida Hosp, Dept Neurol, Iida 3958505, Japan
[4] Hyogo Coll Med, Dept Biochem, Nishinomiya, Hyogo 6638501, Japan
[5] Gifu Pharmaceut Univ, Lab Med Therapeut & Mol Therapeut, Gifu 5011196, Japan
[6] Gifu Univ, Dept Neurol & Geriatr, Grad Sch Med, Gifu 5011194, Japan
关键词
Amyotrophic lateral sclerosis (ALS); Cerebrospinal fluid (CSF); Cu; Zn-superoxide dismutase (SOD1); Protein misfolding; MOTOR-NEURON DISEASE; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; CSF FILTRATION; FAMILIAL FORM; KEY ROLE; SOD1; AGGREGATION; MUTATIONS; COPPER;
D O I
10.1186/s13024-019-0341-5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background A subset of familial forms of amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene coding Cu/Zn-superoxide dismutase (SOD1). Mutant SOD1 proteins are susceptible to misfolding and abnormally accumulated in spinal cord, which is most severely affected in ALS. It, however, remains quite controversial whether misfolding of wild-type SOD1 is involved in more prevalent sporadic ALS (sALS) cases without SOD1 mutations. Methods Cerebrospinal fluid (CSF) from patients including sALS as well as several other neurodegenerative diseases and non-neurodegenerative diseases was examined with an immunoprecipitation assay and a sandwich ELISA using antibodies specifically recognizing misfolded SOD1. Results We found that wild-type SOD1 was misfolded in CSF from all sALS cases examined in this study. The misfolded SOD1 was also detected in CSF from a subset of Parkinson's disease and progressive supranuclear palsy, albeit with smaller amounts than those in sALS. Furthermore, the CSF samples containing the misfolded SOD1 exhibited significant toxicity toward motor neuron-like NSC-34 cells, which was ameliorated by removal of the misfolded wild-type SOD1 with immunoprecipitation. Conclusions Taken together, we propose that misfolding of wild-type SOD1 in CSF is a common pathological process of ALS cases regardless of SOD1 mutations.
引用
收藏
页数:21
相关论文
共 50 条
  • [1] Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis
    Eiichi Tokuda
    Yo-ichi Takei
    Shinji Ohara
    Noriko Fujiwara
    Isao Hozumi
    Yoshiaki Furukawa
    Molecular Neurodegeneration, 14
  • [3] Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?
    Yoshiaki Furukawa
    Eiichi Tokuda
    Translational Neurodegeneration, 9
  • [4] Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?
    Furukawa, Yoshiaki
    Tokuda, Eiichi
    TRANSLATIONAL NEURODEGENERATION, 2020, 9 (01)
  • [5] A misfolded dimer of Cu/Zn-superoxide dismutase leading to pathological oligomerization in amyotrophic lateral sclerosis
    Anzai, Itsuki
    Tokuda, Eiichi
    Mukaiyama, Atsushi
    Akiyama, Shuji
    Endo, Fumito
    Yamanaka, Koji
    Misawa, Hidemi
    Furukawa, Yoshiaki
    PROTEIN SCIENCE, 2017, 26 (03) : 484 - 496
  • [6] Prion-like Properties of Misfolded Cu/Zn-superoxide Dismutase in Amyotrophic Lateral Sclerosis: Update and Perspectives
    Tokuda, Eiichi
    Marklund, Stefan L.
    Furukawa, Yoshiaki
    YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 2019, 139 (07): : 1015 - 1019
  • [7] A seeded propagation of Cu, Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis
    Ogawa, Mariko
    Furukawa, Yoshiaki
    FRONTIERS IN CELLULAR NEUROSCIENCE, 2014, 8
  • [8] Oxidative stress and metal content in blood and cerebrospinal fluid of amyotrophic lateral sclerosis patients with and without a Cu, Zn-superoxide dismutase mutation
    Ihara, Y
    Nobukuni, K
    Takata, H
    Hayabara, T
    NEUROLOGICAL RESEARCH, 2005, 27 (01) : 105 - 108
  • [9] Cu,Zn-superoxide dismutase mutation and apoptotic cell death in amyotrophic lateral sclerosis
    Liu, D
    Bao, F
    JOURNAL OF NEUROCHEMISTRY, 2004, 90 : 140 - 140
  • [10] Heterodimer formation of wild-type and amyotrophic lateral sclerosis-causing mutant Cu/Zn-superoxide dismutase induces toxicity independent of protein aggregation
    Witan, Heidrun
    Kern, Andreas
    Koziollek-Drechsler, Ingrid
    Wade, Rebecca
    Behl, Christian
    Clement, Albrecht M.
    HUMAN MOLECULAR GENETICS, 2008, 17 (10) : 1373 - 1385