Lewy bodies are a hallmark of Parkinson's disease (PD) and other related neurological conditions. Understanding why and how they develop is critical to developing better treatments. A study from The Neuro (Montreal Neurological Institute-Hospital) of McGill University, in collaboration with its Early Drug Discovery Unit, has recreated the growth of Lewy bodies in human neurons and followed their formation to gain important insight into why and how they form.
The scientists published their results in the journal Nature Neuroscience on Oct. 8, 2024. Critically, they find that immune challenge is important for this process, identifying a previously unknown link between the immune system and neurological disease.
Lewy bodies are thought to result from the buildup of misfolded proteins in neurons. Previously, the only way to study them in human neurons was through brain autopsy, which is not ideal because cells break down quickly after death. In this study, neuroscientists used human stem cells to create Lewy bodies in living dopaminergic neurons, the kind of cells especially at risk in PD.
The scientists did this by incubating the neurons with a protein called alpha-synuclein, which is found in Lewy bodies, and coupling it to an immune reaction. The results reveal that Lewy bodies develop only when dopaminergic neurons are exposed to both a rise in alpha-synuclein and an immune stimulation. Without the immune challenge, no Lewy bodies developed.
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