Amyloid-beta peptides are cytotoxic to oligodendrocytes.

J. Xu, S. Chen, Shah-hinan Ahmed, H. Chen, G. Ku, M. P. Goldberg, C. Y. Hsu

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (Abeta), a 39-43 amino acid peptide derived from beta-amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in AD and cerebral amyloid angiopathy. Here we demonstrate that Abeta 1-40 and a truncated fragment, Abeta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. Abeta-induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. Abeta activation of redox-sensitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of Abeta-mediated OLG death suggest that oxidative injury contributes to Abeta cytotoxicity in OLGs. Recent demonstration of Abeta deposition and white matter abnormalities in AD implies a potential pathophysiological role for Abeta-mediated cytotoxicity of OLGs in this neurodegenerative disease.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume21
Issue number1
StatePublished - 2001
Externally publishedYes

Fingerprint

Amyloid beta-Peptides
Oligodendroglia
Alzheimer Disease
Neurodegenerative Diseases
Cerebral Amyloid Angiopathy
NF-kappa B
Amyloid beta-Protein Precursor
Transcription Factor AP-1
DNA Fragmentation
Oxidation-Reduction
Blood Vessels
Dementia
Transcription Factors
Antioxidants
Amino Acids
Peptides
Wounds and Injuries

Cite this

Xu, J., Chen, S., Ahmed, S., Chen, H., Ku, G., Goldberg, M. P., & Hsu, C. Y. (2001). Amyloid-beta peptides are cytotoxic to oligodendrocytes. The Journal of neuroscience : the official journal of the Society for Neuroscience, 21(1).

Amyloid-beta peptides are cytotoxic to oligodendrocytes. / Xu, J.; Chen, S.; Ahmed, Shah-hinan; Chen, H.; Ku, G.; Goldberg, M. P.; Hsu, C. Y.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 21, No. 1, 2001.

Research output: Contribution to journalArticle

Xu, J, Chen, S, Ahmed, S, Chen, H, Ku, G, Goldberg, MP & Hsu, CY 2001, 'Amyloid-beta peptides are cytotoxic to oligodendrocytes.', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 21, no. 1.
Xu, J. ; Chen, S. ; Ahmed, Shah-hinan ; Chen, H. ; Ku, G. ; Goldberg, M. P. ; Hsu, C. Y. / Amyloid-beta peptides are cytotoxic to oligodendrocytes. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001 ; Vol. 21, No. 1.
@article{54c3a3e850874305bba5d5cd7a17b580,
title = "Amyloid-beta peptides are cytotoxic to oligodendrocytes.",
abstract = "Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (Abeta), a 39-43 amino acid peptide derived from beta-amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in AD and cerebral amyloid angiopathy. Here we demonstrate that Abeta 1-40 and a truncated fragment, Abeta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. Abeta-induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. Abeta activation of redox-sensitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of Abeta-mediated OLG death suggest that oxidative injury contributes to Abeta cytotoxicity in OLGs. Recent demonstration of Abeta deposition and white matter abnormalities in AD implies a potential pathophysiological role for Abeta-mediated cytotoxicity of OLGs in this neurodegenerative disease.",
author = "J. Xu and S. Chen and Shah-hinan Ahmed and H. Chen and G. Ku and Goldberg, {M. P.} and Hsu, {C. Y.}",
year = "2001",
language = "English (US)",
volume = "21",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "1",

}

TY - JOUR

T1 - Amyloid-beta peptides are cytotoxic to oligodendrocytes.

AU - Xu, J.

AU - Chen, S.

AU - Ahmed, Shah-hinan

AU - Chen, H.

AU - Ku, G.

AU - Goldberg, M. P.

AU - Hsu, C. Y.

PY - 2001

Y1 - 2001

N2 - Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (Abeta), a 39-43 amino acid peptide derived from beta-amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in AD and cerebral amyloid angiopathy. Here we demonstrate that Abeta 1-40 and a truncated fragment, Abeta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. Abeta-induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. Abeta activation of redox-sensitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of Abeta-mediated OLG death suggest that oxidative injury contributes to Abeta cytotoxicity in OLGs. Recent demonstration of Abeta deposition and white matter abnormalities in AD implies a potential pathophysiological role for Abeta-mediated cytotoxicity of OLGs in this neurodegenerative disease.

AB - Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive dementia. Amyloid-beta peptide (Abeta), a 39-43 amino acid peptide derived from beta-amyloid precursor protein, forms insoluble fibrillar aggregates that have been linked to neuronal and vascular degeneration in AD and cerebral amyloid angiopathy. Here we demonstrate that Abeta 1-40 and a truncated fragment, Abeta 25-35, induced death of oligodendrocytes (OLGs) in vitro in a dose-dependent manner with similar potencies. Abeta-induced OLG death was accompanied by nuclear DNA fragmentation, mitochondrial dysfunction, and cytoskeletal disintegration. Abeta activation of redox-sensitive transcription factors NF-kappaB and AP-1 and antioxidant prevention of Abeta-mediated OLG death suggest that oxidative injury contributes to Abeta cytotoxicity in OLGs. Recent demonstration of Abeta deposition and white matter abnormalities in AD implies a potential pathophysiological role for Abeta-mediated cytotoxicity of OLGs in this neurodegenerative disease.

UR - http://www.scopus.com/inward/record.url?scp=0035227685&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035227685&partnerID=8YFLogxK

M3 - Article

C2 - 11150354

AN - SCOPUS:0035227685

VL - 21

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 1

ER -