IFNAR1 loss links the immune system to Parkinson’s
A protein in brain cells turns out to be critical for Parkinson’s disease.
Researchers studied what happens when the protein IFNAR1 is absent from brain cells in mice. IFNAR1 is a receptor for innate immune signals (interferon-alpha and -beta). The study, published in the Journal of Biomedical Science, shows that loss of this protein leads to mitochondrial dysfunction, disruption of the organelles that produce cellular energy. The result in mice: loss of dopamine-producing neurons, neurodegeneration, and behavioural symptoms resembling Parkinson’s disease with dementia.
Mitophagy as a central mechanism
Without IFNAR1, a process called mitophagy is impaired. Mitophagy is how cells clear out and recycle damaged mitochondria. When it fails, defective energy-producing structures accumulate. This has long been recognised as a risk factor in genetic forms of Parkinson’s. The new finding suggests the same mechanism may also apply in non-genetic cases.
Notably, IFNAR1 expression was found to be reduced in patients with Parkinson’s disease and Lewy Body Dementia compared to healthy controls. That points to human relevance, though this is an association and not proof of causation.
Cell type shapes the outcome
The researchers selectively removed IFNAR1 from either neurons (nerve cells) or astrocytes (support cells in the brain). Neurons without IFNAR1 showed motor and cognitive deficits. Astrocytes without IFNAR1 produced behavioural changes resembling neuropsychiatric disturbances. This suggests the protein plays distinct roles in each cell type during disease progression.
Whether boosting IFNAR1 activity could become a Parkinson’s treatment remains unknown. Further research is needed, but the findings provide a mechanistic foundation for new therapeutic thinking.