Accumulation of human SOD1 and ubiquitinated deposits in the spinal cord of SOD1G93A mice during motor neuron disease progression correlates with a decrease of proteasome

C. Cheroni, M. Peviani, P. Cascio, S. DeBiasi, C. Monti, C. Bendotti

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Mutations in SOD1 cause selective motor neuron degeneration in familial amyotrophic lateral sclerosis patients and transgenic mice overexpressing the mutant enzyme. Formation and accumulation of ubiquitinated aggregates in motor neurons are thought to be involved in the toxic gain of function of mutant SOD1. The present study shows that the accumulation of soluble and detergent-insoluble mutant SOD1 in spinal cord of symptomatic SOD1G93A transgenic mice is due to impaired degradation of mutant SOD1 rather than to increased transcript levels. This effect was accompanied by a decrease of constitutive proteasome levels and a concomitant increase of immunoproteasome in the spinal cord homogenate which resulted in overall unchanged proteasome activity. A decrease of constitutive proteasome occurred in the motor neurons of SOD1G93A mice at the presymptomatic stage and became remarkable with the progression of the disease. This provides further evidence for an involvement of proteasome impairment in the toxicity of mutant SOD1.

Original languageEnglish
Pages (from-to)509-522
Number of pages14
JournalNeurobiology of Disease
Volume18
Issue number3
DOIs
Publication statusPublished - Apr 2005

Fingerprint

Motor Neuron Disease
Proteasome Endopeptidase Complex
Disease Progression
Spinal Cord
Motor Neurons
Transgenic Mice
Nerve Degeneration
Poisons
Detergents
Mutation
Enzymes

Keywords

  • Amyotrophic lateral sclerosis
  • Motor neurons
  • Proteasome
  • Protein aggregates
  • SOD1G93A transgenic mouse model
  • Ubiquitin

ASJC Scopus subject areas

  • Neurology

Cite this

Accumulation of human SOD1 and ubiquitinated deposits in the spinal cord of SOD1G93A mice during motor neuron disease progression correlates with a decrease of proteasome. / Cheroni, C.; Peviani, M.; Cascio, P.; DeBiasi, S.; Monti, C.; Bendotti, C.

In: Neurobiology of Disease, Vol. 18, No. 3, 04.2005, p. 509-522.

Research output: Contribution to journalArticle

@article{e1e2726fda0445fe83d92ac5bcc0478f,
title = "Accumulation of human SOD1 and ubiquitinated deposits in the spinal cord of SOD1G93A mice during motor neuron disease progression correlates with a decrease of proteasome",
abstract = "Mutations in SOD1 cause selective motor neuron degeneration in familial amyotrophic lateral sclerosis patients and transgenic mice overexpressing the mutant enzyme. Formation and accumulation of ubiquitinated aggregates in motor neurons are thought to be involved in the toxic gain of function of mutant SOD1. The present study shows that the accumulation of soluble and detergent-insoluble mutant SOD1 in spinal cord of symptomatic SOD1G93A transgenic mice is due to impaired degradation of mutant SOD1 rather than to increased transcript levels. This effect was accompanied by a decrease of constitutive proteasome levels and a concomitant increase of immunoproteasome in the spinal cord homogenate which resulted in overall unchanged proteasome activity. A decrease of constitutive proteasome occurred in the motor neurons of SOD1G93A mice at the presymptomatic stage and became remarkable with the progression of the disease. This provides further evidence for an involvement of proteasome impairment in the toxicity of mutant SOD1.",
keywords = "Amyotrophic lateral sclerosis, Motor neurons, Proteasome, Protein aggregates, SOD1G93A transgenic mouse model, Ubiquitin",
author = "C. Cheroni and M. Peviani and P. Cascio and S. DeBiasi and C. Monti and C. Bendotti",
year = "2005",
month = "4",
doi = "10.1016/j.nbd.2004.12.007",
language = "English",
volume = "18",
pages = "509--522",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Accumulation of human SOD1 and ubiquitinated deposits in the spinal cord of SOD1G93A mice during motor neuron disease progression correlates with a decrease of proteasome

AU - Cheroni, C.

AU - Peviani, M.

AU - Cascio, P.

AU - DeBiasi, S.

AU - Monti, C.

AU - Bendotti, C.

PY - 2005/4

Y1 - 2005/4

N2 - Mutations in SOD1 cause selective motor neuron degeneration in familial amyotrophic lateral sclerosis patients and transgenic mice overexpressing the mutant enzyme. Formation and accumulation of ubiquitinated aggregates in motor neurons are thought to be involved in the toxic gain of function of mutant SOD1. The present study shows that the accumulation of soluble and detergent-insoluble mutant SOD1 in spinal cord of symptomatic SOD1G93A transgenic mice is due to impaired degradation of mutant SOD1 rather than to increased transcript levels. This effect was accompanied by a decrease of constitutive proteasome levels and a concomitant increase of immunoproteasome in the spinal cord homogenate which resulted in overall unchanged proteasome activity. A decrease of constitutive proteasome occurred in the motor neurons of SOD1G93A mice at the presymptomatic stage and became remarkable with the progression of the disease. This provides further evidence for an involvement of proteasome impairment in the toxicity of mutant SOD1.

AB - Mutations in SOD1 cause selective motor neuron degeneration in familial amyotrophic lateral sclerosis patients and transgenic mice overexpressing the mutant enzyme. Formation and accumulation of ubiquitinated aggregates in motor neurons are thought to be involved in the toxic gain of function of mutant SOD1. The present study shows that the accumulation of soluble and detergent-insoluble mutant SOD1 in spinal cord of symptomatic SOD1G93A transgenic mice is due to impaired degradation of mutant SOD1 rather than to increased transcript levels. This effect was accompanied by a decrease of constitutive proteasome levels and a concomitant increase of immunoproteasome in the spinal cord homogenate which resulted in overall unchanged proteasome activity. A decrease of constitutive proteasome occurred in the motor neurons of SOD1G93A mice at the presymptomatic stage and became remarkable with the progression of the disease. This provides further evidence for an involvement of proteasome impairment in the toxicity of mutant SOD1.

KW - Amyotrophic lateral sclerosis

KW - Motor neurons

KW - Proteasome

KW - Protein aggregates

KW - SOD1G93A transgenic mouse model

KW - Ubiquitin

UR - http://www.scopus.com/inward/record.url?scp=14744302540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14744302540&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2004.12.007

DO - 10.1016/j.nbd.2004.12.007

M3 - Article

C2 - 15755678

AN - SCOPUS:14744302540

VL - 18

SP - 509

EP - 522

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 3

ER -