Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons

Carlos A Pardo-Villamizar, Zuoshang Xu, David R. Borchelt, Donald L. Price, Sangram S. Sisodia, Don W. Cleveland

Research output: Contribution to journalArticle

Abstract

Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.

Original languageEnglish (US)
Pages (from-to)954-958
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number4
DOIs
StatePublished - Feb 14 1995

Fingerprint

Motor Neurons
Dendrites
Superoxide Dismutase
Axons
Neurons
Mutation
Central Nervous System
Substantia Gelatinosa
Cell Body
Superoxide Dismutase-1
Peroxisomes
Pyramidal Cells
Peripheral Nervous System
Interneurons
Cerebral Cortex
Transgenic Mice
Population
Reactive Oxygen Species
Hippocampus
Spinal Cord

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons. / Pardo-Villamizar, Carlos A; Xu, Zuoshang; Borchelt, David R.; Price, Donald L.; Sisodia, Sangram S.; Cleveland, Don W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 4, 14.02.1995, p. 954-958.

Research output: Contribution to journalArticle

@article{33b30cbbcdf947389e0ee97fb5445de8,
title = "Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons",
abstract = "Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.",
author = "Pardo-Villamizar, {Carlos A} and Zuoshang Xu and Borchelt, {David R.} and Price, {Donald L.} and Sisodia, {Sangram S.} and Cleveland, {Don W.}",
year = "1995",
month = "2",
day = "14",
doi = "10.1073/pnas.92.4.954",
language = "English (US)",
volume = "92",
pages = "954--958",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "4",

}

TY - JOUR

T1 - Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons

AU - Pardo-Villamizar, Carlos A

AU - Xu, Zuoshang

AU - Borchelt, David R.

AU - Price, Donald L.

AU - Sisodia, Sangram S.

AU - Cleveland, Don W.

PY - 1995/2/14

Y1 - 1995/2/14

N2 - Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.

AB - Mutation in superoxide dismutase 1 (SOD1), a Cu/Zn enzyme that removes oxygen radicals and protects against oxidative injury, has been implicated in some cases of familial amyotrophic lateral sclerosis (FALS). As a first approach to examining the mechanism(s) through which these mutations cause specific degeneration of motor neurons, we have used immunocytochemistry to identify the distribution of SOD1 in populations of cells in the peripheral and central nervous systems. In the spinal cord, intense SOD1 immunoreactivity was present in motor neurons, interneurons, and substantia gelatinosa. In motor neurons, SOD1 immunoreactivity was abundant in perikarya, dendrites, and axons; most of this activity appeared to be free in the cytoplasm, although a portion was associated with membranous vesicles, presumably peroxisomes. Since a variety of central nervous system neurons, including pyramidal cells in cerebral cortex and neurons of the CA3 and CA4 sectors of the hippocampus, showed high immunoreactivity but are unaffected in ALS, the apparent abundance of SOD1 does not predict vulnerability of neurons to mutations in SOD1. Rather, SOD1 accumulates in many neuronal populations but is particularly abundant in motor neurons. Consistent with recent studies of FALS-linked SOD1 mutations in vitro and in transgenic mice, our findings offer further support for the view that the mutations confer a gain of adverse function. In this view, high, rather than limiting, levels of SOD1 may place motor neurons selectively at risk in FALS.

UR - http://www.scopus.com/inward/record.url?scp=0028815433&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028815433&partnerID=8YFLogxK

U2 - 10.1073/pnas.92.4.954

DO - 10.1073/pnas.92.4.954

M3 - Article

VL - 92

SP - 954

EP - 958

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 4

ER -