Abstract
This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American 'C' family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single site GCC to GTC substitution at codon 4 (Ala4 → Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 481-490 |
| Number of pages | 10 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 55 |
| Issue number | 4 |
| State | Published - Apr 1996 |
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Keywords
- Amyotrophic lateral sclerosis
- Anterior horn cells
- Gene analysis
- Immunoelectron microscopy
- Immunohistochemistry
- Intracytoplasmic hyaline inclusions
- Superoxide dismutase
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Neuroscience(all)
Cite this
Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement. / Shibata, Noriyuki; Hirano, Asao; Kobayashi, Makio; Siddique, Teepu; Deng, Han Xiang; Hung, Wu Yen; Kato, Takeo; Asayama, Kohtaro.
In: Journal of Neuropathology and Experimental Neurology, Vol. 55, No. 4, 04.1996, p. 481-490.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement
AU - Shibata, Noriyuki
AU - Hirano, Asao
AU - Kobayashi, Makio
AU - Siddique, Teepu
AU - Deng, Han Xiang
AU - Hung, Wu Yen
AU - Kato, Takeo
AU - Asayama, Kohtaro
PY - 1996/4
Y1 - 1996/4
N2 - This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American 'C' family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single site GCC to GTC substitution at codon 4 (Ala4 → Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.
AB - This report concerns retrospective immunohistochemical and immunoelectron microscopic studies on superoxide dismutase-1 (SOD1) in intracytoplasmic hyaline inclusions (IHIs) of the anterior horn cells of three patients with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement. All of the patients were members of the American 'C' family. Almost all of the IHIs, present in the soma and cordlike swollen neurites of some affected neurons of the three patients, were intensely stained by an antibody to human SOD1. By contrast, the cytoplasm of anterior horn cells of the ALS patients and of ten control individuals reacted only weakly with the antibody or not at all. Immunoelectron microscopy revealed that the granule associated thick linear structures that composed the IHIs were intensely labeled by the antibody to SOD1. The IHIs were also positively stained by antibodies to ubiquitin and phosphorylated neurofilament protein, with the distribution of immunoreactivity resembling that seen with the anti-SOD1 antibody. The DNA analysis disclosed a single site GCC to GTC substitution at codon 4 (Ala4 → Val) in the SOD1 gene from the brain samples of the patients and from the peripheral blood of their family members. Our results suggest that SOD1 is a component of IHIs and may interact with ubiquitin and neurofilament protein, and point to the possibility that the presence of intense SOD1 immunoreactivity in the IHIs may be of relevance in processes involving structurally altered SOD1 molecules encoded by the mutated gene.
KW - Amyotrophic lateral sclerosis
KW - Anterior horn cells
KW - Gene analysis
KW - Immunoelectron microscopy
KW - Immunohistochemistry
KW - Intracytoplasmic hyaline inclusions
KW - Superoxide dismutase
UR - http://www.scopus.com/inward/record.url?scp=0029927679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029927679&partnerID=8YFLogxK
M3 - Article
C2 - 8786408
AN - SCOPUS:0029927679
VL - 55
SP - 481
EP - 490
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 4
ER -