Researchers reveal novel mechanism that links interferon activation and α-synuclein function in neurons

There are no disease-modifying therapies for Parkinson’s disease that can alter the course of the disease. The University of Colorado Anschutz Medical Campus faculty is leading a group of scientists from around the world who are working to change that.

Researchers reveal novel mechanism that links interferon activation and α-synuclein function in neurons

Image Credit: University of Colorado Anschutz Medical Campus.

The researchers published their findings in the journal Brain which takes researchers one step closer to realizing α-synuclein (αSyn), a crucial protein that they identified links inflammation and Parkinson’s disease.

Neurodegenerative diseases like Parkinson’s disease and dementia with Lewy bodies are linked to the protein αSyn, which is mainly expressed in neurons. This new study points to a novel mechanism as a potential precursor to Parkinson’s disease that connects interferon activation and αSyn function in neurons.

It’s critical to understand further the triggers that contribute to the development of Parkinson’s disease and how inflammation may interact with proteins found in the disease. With this information, we could potentially provide new approaches for treatments by altering or interfering with these inflammatory pathways that may act as a trigger for the disease.”

David Beckham MD, Associate Professor, Department of Infectious Disease, University of Colorado School of Medicine, CU Anschutz Medical Campus

Link could play role in PD development

The investigators challenged αSyn knock-out (KO) mice and human αSyn KO dopaminergic neurons with RNA virus infection to assess the mechanism of αSyn-induced immune responses to viral infections in the brain.

They found that αSyn is essential for the neuronal expression of interferon-stimulated genes (ISGs). They then discovered that αSyn interacts with signaling proteins in neurons to induce expression of ISGs in response to any stimulus that induces interferon signals, a type of immune response.

Inflammation and αSyn, a protein closely linked to the onset of Parkinson’s disease, are now clearly linked for the first time by this research.

The data, according to the authors, confirms that αSyn reacts to inflammatory and infectious pathways, and it raises the possibility that this interaction may be crucial for the onset of Parkinson’s disease. The next critical step is to ascertain whether interactions between αSyn and interferon cause the toxic forms of misfolded αSyn known as fibrils to form, which have been linked to Parkinson’s disease.

Future research, according to the researchers, is required to examine the interactions between type 1 interferon signals in neurons and misfolded αSyn to ascertain whether medications that block these interactions can stop the development of misfolded αSyn. A potential disease-modifying therapeutic strategy would emerge as a result, which patients would require.

Source:
Journal reference:

Monogue, B., et al. (2022) Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue. Brain. doi.org/10.1093/brain/awac192.

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