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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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; Friis Rundsten, Carsten; Ruscher, Karsten; Pakkenberg, Bente; Goldmann, Tobias; Loreth, Desiree; Prinz, Marco; Rubinsztein, David C; Issazadeh-Navikas, Shohreh.

In: Cell, Vol. 163, No. 2, 2015, p. 324-39.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Ejlerskov, P, Hultberg, JG, Wang, J, Carlsson, R, Ambjørn, M, Kuss, M, Liu, Y, Porcu, G, Kolkova, K, Friis Rundsten, C, Ruscher, K, Pakkenberg, B, Goldmann, T, Loreth, D, Prinz, M, Rubinsztein, DC & Issazadeh-Navikas, S 2015, 'Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia', Cell, vol. 163, no. 2, pp. 324-39. https://doi.org/10.1016/j.cell.2015.08.069

APA

Ejlerskov, P., Hultberg, J. G., Wang, J., Carlsson, R., Ambjørn, M., Kuss, M., Liu, Y., Porcu, G., Kolkova, K., Friis Rundsten, C., Ruscher, K., Pakkenberg, B., Goldmann, T., Loreth, D., Prinz, M., Rubinsztein, D. C., & Issazadeh-Navikas, S. (2015). Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia. Cell, 163(2), 324-39. https://doi.org/10.1016/j.cell.2015.08.069

Vancouver

Ejlerskov P, Hultberg JG, Wang J, Carlsson R, Ambjørn M, Kuss M et al. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia. Cell. 2015;163(2):324-39. https://doi.org/10.1016/j.cell.2015.08.069

Author

Ejlerskov, Patrick ; Hultberg, Jeanette Göransdotter ; Wang, JunYang ; Carlsson, Robert ; Ambjørn, Malene ; Kuss, Martin ; Liu, Yawei ; Porcu, Giovanna ; Kolkova, Kateryna ; Friis Rundsten, Carsten ; Ruscher, Karsten ; Pakkenberg, Bente ; Goldmann, Tobias ; Loreth, Desiree ; Prinz, Marco ; Rubinsztein, David C ; Issazadeh-Navikas, Shohreh. / Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia. In: Cell. 2015 ; Vol. 163, No. 2. pp. 324-39.

Bibtex

@article{778cded361bc4c788e480053a82b8e62,
title = "Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia",
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 = "Patrick Ejlerskov and Hultberg, {Jeanette G{\"o}ransdotter} and JunYang Wang and Robert Carlsson and Malene Ambj{\o}rn and Martin Kuss and Yawei Liu and Giovanna Porcu and Kateryna Kolkova and {Friis Rundsten}, Carsten and Karsten Ruscher and Bente Pakkenberg and Tobias Goldmann and Desiree Loreth and Marco Prinz and Rubinsztein, {David C} and Shohreh Issazadeh-Navikas",
note = "Copyright {\textcopyright} 2015 Elsevier Inc. All rights reserved.",
year = "2015",
doi = "10.1016/j.cell.2015.08.069",
language = "English",
volume = "163",
pages = "324--39",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia

AU - Ejlerskov, Patrick

AU - Hultberg, Jeanette Göransdotter

AU - Wang, JunYang

AU - Carlsson, Robert

AU - Ambjørn, Malene

AU - Kuss, Martin

AU - Liu, Yawei

AU - Porcu, Giovanna

AU - Kolkova, Kateryna

AU - Friis Rundsten, Carsten

AU - Ruscher, Karsten

AU - Pakkenberg, Bente

AU - Goldmann, Tobias

AU - Loreth, Desiree

AU - Prinz, Marco

AU - Rubinsztein, David C

AU - Issazadeh-Navikas, Shohreh

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1016/j.cell.2015.08.069

DO - 10.1016/j.cell.2015.08.069

M3 - Journal article

C2 - 26451483

VL - 163

SP - 324

EP - 339

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -

ID: 145702511