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Region Hovedstaden - en del af Københavns Universitetshospital
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Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia

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  • Patrick Ejlerskov
  • Jeanette Göransdotter Hultberg
  • JunYang Wang
  • Robert Carlsson
  • Malene Ambjørn
  • Martin Kuss
  • Yawei Liu
  • Giovanna Porcu
  • Kateryna Kolkova
  • Carsten Friis Rundsten
  • Karsten Ruscher
  • Bente Pakkenberg
  • Tobias Goldmann
  • Desiree Loreth
  • Marco Prinz
  • David C Rubinsztein
  • Shohreh Issazadeh-Navikas
Vis graf over relationer

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.

OriginalsprogEngelsk
TidsskriftCell
Vol/bind163
Udgave nummer2
Sider (fra-til)324-39
Antal sider16
ISSN0092-8674
DOI
StatusUdgivet - 8 okt. 2015

ID: 45846033