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Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia.

Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang; Carlsson, Robert; Ambjørn, Malene; Kuss, Martin; Liu, Yawei; Porcu, Giovanna; Kolkova, Kateryna and Friis Rundsten, Carsten, et al. (2015) In Cell 163(2). p.324-339
Abstract
Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β... (More)
Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β promoted neurite growth and branching, autophagy flux, and α-synuclein degradation in neurons. In addition, lentiviral IFN-β overexpression prevented dopaminergic neuron loss in a familial Parkinson's disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson's disease dementia. (Less)
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published
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Cell
volume
163
issue
2
pages
324 - 339
publisher
Cell Press
external identifiers
  • pmid:26451483
  • wos:000362952700011
  • scopus:84943638074
ISSN
1097-4172
DOI
10.1016/j.cell.2015.08.069
language
English
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yes
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a7fbaf81-075f-43eb-b8ef-f6e9f8b327ec (old id 8158459)
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http://www.ncbi.nlm.nih.gov/pubmed/26451483?dopt=Abstract
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2015-11-02 21:42:06
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2017-11-19 03:09:44
@article{a7fbaf81-075f-43eb-b8ef-f6e9f8b327ec,
  abstract     = {Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β promoted neurite growth and branching, autophagy flux, and α-synuclein degradation in neurons. In addition, lentiviral IFN-β overexpression prevented dopaminergic neuron loss in a familial Parkinson's disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson's disease dementia.},
  author       = {Ejlerskov, Patrick and Hultberg, Jeanette Göransdotter and Wang, JunYang and Carlsson, Robert and Ambjørn, Malene and Kuss, Martin and Liu, Yawei and Porcu, Giovanna and Kolkova, Kateryna and Friis Rundsten, Carsten and Ruscher, Karsten and Pakkenberg, Bente and Goldmann, Tobias and Loreth, Desiree and Prinz, Marco and Rubinsztein, David C and Issazadeh-Navikas, Shohreh},
  issn         = {1097-4172},
  language     = {eng},
  number       = {2},
  pages        = {324--339},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia.},
  url          = {http://dx.doi.org/10.1016/j.cell.2015.08.069},
  volume       = {163},
  year         = {2015},
}