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

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.

Hultberg, Jeanette Göransdotter (author)
Wang, JunYang (author)
Carlsson, Robert (author)
Ambjørn, Malene (author)
Kuss, Martin (author)
Liu, Yawei (author)
Porcu, Giovanna (author)
Kolkova, Kateryna (author)
Friis Rundsten, Carsten (author)
Ruscher, KarstenLund University,Lunds universitet,Neurokirurgi,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurosurgery,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-ktr (author)
Pakkenberg, Bente (author)
Goldmann, Tobias (author)
Loreth, Desiree (author)
Prinz, Marco (author)
Rubinsztein, David C (author)
Issazadeh-Navikas, Shohreh (author)
NeurokirurgiSektion IV (creator_code:org_t)

By the author/editor: Ejlerskov, Patri ...; Hultberg, Jeanet ...; Wang, JunYang; Carlsson, Robert; Ambjørn, Malene; Kuss, Martin; show more...; Liu, Yawei; Porcu, Giovanna; Kolkova, Kateryn ...; Friis Rundsten, ...; Ruscher, Karsten; Pakkenberg, Bent ...; Goldmann, Tobias; Loreth, Desiree; Prinz, Marco; Rubinsztein, Dav ...; Issazadeh-Navika ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

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