Proteolytic activity in amyotrophic lateral sclerosis IgG preparations
- 1 November 1996
- journal article
- research article
- Published by Wiley in Annals of Neurology
- Vol. 40 (5) , 701-706
- https://doi.org/10.1002/ana.410400505
Abstract
Sporadic amyotrophic lateral sclerosis is a motor neuron disease of unknown origin. Autoimmunity against voltagegated calcium channels is one mechanism hypothesized to be the cause of the disease. In support of this hypothesis, it was previously reported that amyotrophic lateral sclerosis IgG specifically blocked the binding of 8B7 monoclonal antibody to the α1 subunit of voltage‐gated calcium channels, suggesting overlapping epitopes of the two antibodies. It is, however, possible that the 8B7 epitope was destroyed by proteases. Data presented here show that the blocking of 8B7 binding to the α1 subunit by diethylaminoethyl cellulose (DEAE)‐purified amyotrophic lateral sclerosis IgG was not observed with Fab fragments of amyotrophic lateral sclerosis IgG. The blocking was prevented by serine protease inhibitors. Moreover, it was reproduced by plaminogen and urokinase. These observations suggest that raised proteolytic activity in amyotrophic lateral sclerosis IgG preparations may be responsible for the blockade of 8B7 monoclonal antibody demonstrated previously. They also indicate the need to be particularly cautious when interpreting the results of incubation in amyotrophic lateral sclerosis sera or IgG preparations. Furthermore, they suggest that proteases may be partly responsible for some of the effects previously described for amyotrophic lateral sclerosis IgG. However, the proteolytic activity needs to be better defined and its possible role in amyotrophic lateral sclerosis investigated.Keywords
This publication has 26 references indexed in Scilit:
- Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral SclerosisScience, 1996
- Can Neurotrophic Factors Prevent or Reverse Motoneuron Injury in Amyotrophic Lateral Sclerosis?Experimental Neurology, 1993
- Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: A mouse model of amyotrophic lateral sclerosisCell, 1993
- Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosisNature, 1993
- Decreased Glutamate Transport by the Brain and Spinal Cord in Amyotrophic Lateral SclerosisNew England Journal of Medicine, 1992
- Linkage of a Gene Causing Familial Amyotrophic Lateral Sclerosis to Chromosome 21 and Evidence of Genetic-Locus HeterogeneityNew England Journal of Medicine, 1991
- The neuroexcitotoxic amino acids glutamate and aspartate are altered in the spinal cord and brain in amyotrophic lateral sclerosisAnnals of Neurology, 1988
- Familial adult motor neuron disease: amyotrophic lateralsclerosisNeurology, 1986
- A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and alzheimer diseaseAnnals of Neurology, 1981
- Neuromuscular junction macromolecules in the pathogenesis of amyotrophic lateral sclerosisMedical Hypotheses, 1980