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Phosphorylation of Neurofilaments Is Altered in Amyotrophic Lateral Sclerosis

Phosphorylation of Neurofilaments Is Altered in Amyotrophic Lateral Sclerosis Abstract We used a library of monoclonal antibodies (Mab) that distinguish phosphorylated (P+) and non-phosphorylated (P−) neurofilament (NF) epitopes to examine phosphorylation of NF in lower motor neurons of patients with amyotrophic lateral sclerosis (ALS), of neurologically normal controls of different ages, and of patients with central chromatolysis due to injuries to motor root axons. Monoclonal antibodies directed to P+ NF immunostained five to ten times more neuronal perikarya in ALS than in age-matched controls. Spheroids, which are NF containing axonal enlargements, found in significantly greater number in proximal axons in ALS, were also intensely immunostained with Mab to P+ NF. Moreover, anterior root axons in five of eleven cases of ALS reacted only with the Mab to P+ NF, while both P− and P+ NF were present in motor roots from controls. In control groups, the number of neuronal perikarya and spheroids that immunoreacted with the Mab to P+ NF increased moderately with age. Chromatolytic lower motor neurons were recognized by Mab to P+ NF. Our results show that the process of phosphorylation is altered in ALS. We propose that phosphorylation of NF in ALS occurs prematurely and that it is more likely to be associated with an impairment of NF transport than to be part of a chromatolytic reaction of lower motor neurons. Amyotrophic lateral sclerosis, Axonal transport, Central chromatolysis, Neurofilament, Phosphorylation This content is only available as a PDF. Author notes Supported by National Institutes of Health Grants AG 00795 and NS 14503 and the David S. Ingalls Fund. Dr. Manetto is a recipient of a fellowship from the Britton Fund. Copyright © 1988 by the American Association of Neuropathologists http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuropathology & Experimental Neurology Oxford University Press

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Publisher
Oxford University Press
Copyright
Copyright © 1988 by the American Association of Neuropathologists
ISSN
0022-3069
eISSN
1554-6578
DOI
10.1097/00005072-198811000-00007
Publisher site
See Article on Publisher Site

Abstract

Abstract We used a library of monoclonal antibodies (Mab) that distinguish phosphorylated (P+) and non-phosphorylated (P−) neurofilament (NF) epitopes to examine phosphorylation of NF in lower motor neurons of patients with amyotrophic lateral sclerosis (ALS), of neurologically normal controls of different ages, and of patients with central chromatolysis due to injuries to motor root axons. Monoclonal antibodies directed to P+ NF immunostained five to ten times more neuronal perikarya in ALS than in age-matched controls. Spheroids, which are NF containing axonal enlargements, found in significantly greater number in proximal axons in ALS, were also intensely immunostained with Mab to P+ NF. Moreover, anterior root axons in five of eleven cases of ALS reacted only with the Mab to P+ NF, while both P− and P+ NF were present in motor roots from controls. In control groups, the number of neuronal perikarya and spheroids that immunoreacted with the Mab to P+ NF increased moderately with age. Chromatolytic lower motor neurons were recognized by Mab to P+ NF. Our results show that the process of phosphorylation is altered in ALS. We propose that phosphorylation of NF in ALS occurs prematurely and that it is more likely to be associated with an impairment of NF transport than to be part of a chromatolytic reaction of lower motor neurons. Amyotrophic lateral sclerosis, Axonal transport, Central chromatolysis, Neurofilament, Phosphorylation This content is only available as a PDF. Author notes Supported by National Institutes of Health Grants AG 00795 and NS 14503 and the David S. Ingalls Fund. Dr. Manetto is a recipient of a fellowship from the Britton Fund. Copyright © 1988 by the American Association of Neuropathologists

Journal

Journal of Neuropathology & Experimental NeurologyOxford University Press

Published: Nov 1, 1988

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