Cited by 301Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsNuclear Receptors and Signaling

Mouse Model of Multiple System Atrophy α-Synuclein Expression in Oligodendrocytes Causes Glial and Neuronal Degeneration

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Yazawa, Ikuru, Giasson, Benoit I., Sasaki, Ryogen, Zhang, Bin, Joyce, Sonali, Uryu, Kunihiro, Trojanowski, John Q., Lee, Virginia M.-Y.·2005·Neuron

Abstract

Transgenic (Tg) mice overexpressing human wild-type alpha-synuclein in oligodendrocytes under the control of the 2,' 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) promoter are shown here to recapitulate features of multiple system atrophy (MSA), including the accumulation of filamentous human alpha-synuclein aggregates in oligodendrocytes linked to their degeneration and autophagocytosis of myelin. Significantly, endogenous mouse alpha-synuclein also accumulated in normal and degenerating axons and axon terminals in association with oligodendroglia and neuron loss and slowly progressive motor impairments. Our studies demonstrate that overexpression of alpha-synuclein in oligodendrocytes of mice results in MSA-like degeneration in the CNS and that alpha-synuclein inclusions in oligodendrocytes participate in the degeneration of neurons in MSA.

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Crossref · 10.1016/j.neuron.2005.01.032

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Authors
Yazawa, I., Giasson, B. I., Sasaki, R., Zhang, B., Joyce, S., Uryu, K., Trojanowski, J. Q., & Lee, V. M.-Y.
Affiliations
University of Pennsylvania (US)
Corresponding author
Lee, Virginia M.-Y.
Venue
Neuron
Publisher
Elsevier BV
Published
2005-03
Volume
45
Issue
6
Pages
847-859
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1980110509
Cited by
301
References
47
Citations by year
2026: 7 · 2025: 6 · 2024: 12 · 2023: 6 · 2022: 7 · 2021: 17 · 2020: 13 · 2019: 19 · 2018: 13 · 2017: 16 · 2016: 9 · 2015: 11 · 2014: 21 · 2013: 22 · 2012: 9
FWCI
11.23
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Canadian Institutes of Health Research
  • National Institutes of Health (AG-09215, NS-044233)
  • Naito Foundation
  • Okinaka Memorial Institute for Medical Research
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
multiple system atrophy, alpha-synuclein, oligodendrocytes, transgenic mouse model, oligodendrocyte degeneration, neurodegeneration, motor impairment, glial degeneration
MeSH terms
Animals, Axons, Inclusion Bodies, Central Nervous System, Disease Models, Animal, Humans, Mice, Transgenic, Myelin Sheath, Nerve Tissue Proteins, Neuroglia, Neurons, Oligodendroglia, Phagocytosis, Phosphoric Diester Hydrolases, Promoter Regions, Genetic, Wallerian Degeneration, Presynaptic Terminals, Multiple System Atrophy, Microscopy, Electron, Transmission, Mice, Synucleins, alpha-Synuclein, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase

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