| First Author | Ejlerskov P | Year | 2015 |
| Journal | Cell | Volume | 163 |
| Issue | 2 | Pages | 324-39 |
| PubMed ID | 26451483 | Mgi Jnum | J:226090 |
| Mgi Id | MGI:5695780 | Doi | 10.1016/j.cell.2015.08.069 |
| Citation | Ejlerskov P, et al. (2015) Lack of Neuronal IFN-beta-IFNAR Causes Lewy Body- and Parkinson's Disease-like Dementia. Cell 163(2):324-39 |
| abstractText | 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-beta (IFN-beta) 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 alpha-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-beta signaling caused defects in neuronal autophagy prior to alpha-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-beta promoted neurite growth and branching, autophagy flux, and alpha-synuclein degradation in neurons. In addition, lentiviral IFN-beta overexpression prevented dopaminergic neuron loss in a familial Parkinson's disease model. These results indicate a protective role for IFN-beta in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson's disease dementia. |
