Lab-grown brain cells help uncover new targets for Parkinson鈥檚 treatments
Scientists have uncovered a new link between the immune system and the development of Parkinson鈥檚 disease.
Researchers at The Neuro (Montreal Neurological Institute-Hospital) at 平特五不中 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鈥檚, as previous research has found, but drive its development.
鈥淥ur findings suggest anyone can develop Parkinson鈥檚 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鈥檚 and other neurological diseases,鈥� said senior author Peter McPherson, Distinguished James 平特五不中 Professor of Neurology and Neurosurgery and Anatomy and Cell Biology at The Neuro. His team worked in collaboration with The Neuro鈥檚 Early Drug Discovery Unit.
, 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 伪-synuclein and an immune response. Lewy bodies formed only in dopamine-producing neurons, the brain cells affected in Parkinson鈥檚, and not in other neurons.
Until now, Lewy bodies in human neurons could only be studied post-mortem, limiting researchers鈥� 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鈥檚 disease, which has no cure and affects over 100,000 Canadians.
More evidence of immune system鈥檚 important role
鈥淭he results support previous research showing that an immune response plays an important role in Parkinson鈥檚 development,鈥� said Armin Bayati, a PhD candidate in McPherson鈥檚 lab and the study鈥檚 first author. 鈥淔uture studies should focus on understanding how inflammation caused by an overexcited immune system causes Lewy body formation when coupled with 伪-synuclein.鈥�
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 Qu茅bec - Sant茅.
About the study
"" by Peter McPherson and Armin Bayati et al. was published in Nature Neuroscience.
