TY - JOUR
T1 - Advanced glycation endproducts are deposited in neuronal hyaline inclusions
T2 - A study on familial amyotrophic lateral sclerosis with superoxide dismutase-1 mutation
AU - Shibata, Noriyuki
AU - Hirano, Asao
AU - Kato, Shinsuke
AU - Nagai, Ryoji
AU - Horiuchi, Seikoh
AU - Komori, Takashi
AU - Umahara, Takahiko
AU - Asayama, Kohtaro
AU - Kobayashi, Makio
PY - 1999/3
Y1 - 1999/3
N2 - To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-l (SOD1) mutation, we investigated the immunohistochemical localization of Nε-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Inmunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.
AB - To determine the role of advanced glycation endproducts (AGE) in the pathogenesis of familial amyotrophic lateral sclerosis (ALS) with superoxide dismutase-l (SOD1) mutation, we investigated the immunohistochemical localization of Nε-carboxymethyl-lysine (CML), one of the major AGE structures, in spinal cords from three familial ALS patients with a heterozygous Ala to Val substitution at codon 4 in the gene for SOD1. Neuronal hyaline inclusions (NHIs), the abnormal structures seen in some of the remaining lower motor neurons of familial ALS patients with SOD1 mutation, were intensely stained by a monoclonal antibody specific for CML in contrast to the only weakly stained cytoplasm. Inmunoelectron microscopy depicted the CML determinants restricted to the granule-associated thick linear structures that mainly compose the NHIs. The NHIs were also recognized by antibodies to SOD1, phosphorylated neurofilament protein and ubiquitin. No focal collection of either CML or SOD1 was found in neurons of the control individuals. Our results indicate that CML is a component of the NHIs of familial ALS patients with SOD1 mutation, and suggest that the CML formation may be mediated by protein glycoxidation or lipid peroxidation in the presence of oxidative stress from mutant SOD1, in association with motor neuron degeneration.
KW - Advanced glycation endproducts
KW - Amyotrophic lateral sclerosis
KW - Hyaline inclusions
KW - Immunohistochemistry
KW - Superoxide dismutase
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U2 - 10.1007/s004010050980
DO - 10.1007/s004010050980
M3 - Article
C2 - 10090670
AN - SCOPUS:0032980525
SN - 0001-6322
VL - 97
SP - 240
EP - 246
JO - Acta neuropathologica
JF - Acta neuropathologica
IS - 3
ER -