Scientists have uncovered a new link between the immune system and the development of Parkinson's disease.
Researchers at The Neuro (Montreal Neurological Institute-Hospital) at McGill University have discovered that an immune response plays a key role in how toxic protein clumps, known as Lewy bodies, form in brain cells and contribute to disease.
This suggests factors that trigger the immune system, such as chronic inflammation, exposure to toxins, or prolonged stress may not only correlate with Parkinson's, as previous research has found, but drive its development.
"Our findings suggest anyone can develop Parkinson's if exposed to the right environment, and so a genetic predisposition to disease may not be necessary. This marks a significant step forward to understanding key aspects of Parkinson's and other neurological diseases," said senior author Peter McPherson, Distinguished James McGill Professor of Neurology and Neurosurgery and Anatomy and Cell Biology at The Neuro. His team worked in collaboration with The Neuro's Early Drug Discovery Unit.
The findings, published in Nature Neuroscience, open new possibilities for therapies aimed at managing immune responses, he added.
Recreating a hallmark of Parkinson's disease
For the first time, researchers recreated Lewy bodies in living human neurons derived from stem cells. They watched the protein clusters form in real-time and identified the exact conditions needed: the presence of a protein called α-synuclein and an immune response. Lewy bodies formed only in dopamine-producing neurons, the brain cells affected in Parkinson's, and not in other neurons.
Until now, Lewy bodies in human neurons could only be studied post-mortem, limiting researchers' ability to understand them.
The researchers also discovered that Lewy bodies contain additional cell parts, not just misfolded proteins as previously thought. This advanced understanding of their composition, and the ability to study their formation in real time, could provide drug developers with new targets for slowing the progression of Parkinson's disease, which has no cure and affects over 100,000 Canadians.
More evidence of immune system's important role
"The results support previous research showing that an immune response plays an important role in Parkinson's development," said Armin Bayati, a PhD candidate in McPherson's lab and the study's first author. "Future studies should focus on understanding how inflammation caused by an overexcited immune system causes Lewy body formation when coupled with α-synuclein."
The study was funded by the Canada First Research Excellence Fund; Healthy Brain, Healthy Lives; the Canadian Institutes for Health Research, and Fonds de recherche du Québec - Santé.
About the study
"Modeling Parkinson's disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines" by Peter McPherson and Armin Bayati et al. was published in Nature Neuroscience.
