Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral Sclerosis

被引:18
|
作者
Furukawa, Yoshiaki [1 ]
机构
[1] Keio Univ, Dept Chem, Lab Mech Chem Biomol, Kohoku Ku, 3-14-1 Hiyoshi, Yokohama, Kanagawa 2238522, Japan
关键词
D O I
10.1155/2012/323261
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dominant mutations in a Cu, Zn-superoxide dismutase (SOD1) gene cause a familial form of amyotrophic lateral sclerosis (ALS). While it remains controversial how SOD1 mutations lead to onset and progression of the disease, many in vitro and in vivo studies have supported a gain-of-toxicity mechanism where pathogenic mutations contribute to destabilizing a native structure of SOD1 and thus facilitate misfolding and aggregation. Indeed, abnormal accumulation of SOD1-positive inclusions in spinal motor neurons is a pathological hallmark in SOD1-related familial ALS. Furthermore, similarities in clinical phenotypes and neuropathology of ALS cases with and without mutations in sod1 gene have implied a disease mechanism involving SOD1 common to all ALS cases. Although pathogenic roles of wild-type SOD1 in sporadic ALS remain controversial, recent developments of novel SOD1 antibodies have made it possible to characterize wild-type SOD1 under pathological conditions of ALS. Here, I have briefly reviewed recent progress on biochemical and immunohistochemical characterization of wild-type SOD1 in sporadic ALS cases and discussed possible involvement of wild-type SOD1 in a pathomechanism of ALS.
引用
收藏
页数:6
相关论文
共 50 条
  • [1] Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?
    Yoshiaki Furukawa
    Eiichi Tokuda
    [J]. Translational Neurodegeneration, 9
  • [2] Does wild-type Cu/Zn-superoxide dismutase have pathogenic roles in amyotrophic lateral sclerosis?
    Furukawa, Yoshiaki
    Tokuda, Eiichi
    [J]. TRANSLATIONAL NEURODEGENERATION, 2020, 9 (01)
  • [3] 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
    [J]. Molecular Neurodegeneration, 14
  • [4] Wild-type Cu/Zn-superoxide dismutase is misfolded in cerebrospinal fluid of sporadic amyotrophic lateral sclerosis
    Tokuda, Eiichi
    Takei, Yo-ichi
    Ohara, Shinji
    Fujiwara, Noriko
    Hozumi, Isao
    Furukawa, Yoshiaki
    [J]. MOLECULAR NEURODEGENERATION, 2019, 14 (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
    [J]. PROTEIN SCIENCE, 2017, 26 (03) : 484 - 496
  • [6] Immunochemical characterization on pathological oligomers of mutant Cu/Zn-superoxide dismutase in amyotrophic lateral sclerosis
    Eiichi Tokuda
    Itsuki Anzai
    Takao Nomura
    Keisuke Toichi
    Masahiko Watanabe
    Shinji Ohara
    Seiji Watanabe
    Koji Yamanaka
    Yuta Morisaki
    Hidemi Misawa
    Yoshiaki Furukawa
    [J]. Molecular Neurodegeneration, 12
  • [8] A seeded propagation of Cu, Zn-superoxide dismutase aggregates in amyotrophic lateral sclerosis
    Ogawa, Mariko
    Furukawa, Yoshiaki
    [J]. FRONTIERS IN CELLULAR NEUROSCIENCE, 2014, 8
  • [9] Cu,Zn-superoxide dismutase mutation and apoptotic cell death in amyotrophic lateral sclerosis
    Liu, D
    Bao, F
    [J]. 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.
    [J]. HUMAN MOLECULAR GENETICS, 2008, 17 (10) : 1373 - 1385