A study conducted by researchers at the Perelman School of Medicine, published in Nature, reveals that a malformed protein produces different Parkinson’s-related disorders in response to the kind of cell in which it is embedded.
Conducted in an animal model, the research focused on malformed α-synuclein (α-syn) proteins, which form clumps within brain cells and are absorbed by healthy neurons and replicated. It’s the distinct cell environment, researchers found, that dictates how the clumps “seed” and what kind of disorder results.
In Parkinson’s disorders and 50 percent of Alzheimer’s disease patients, α-syn aggregates in neurons as Lewy bodies. In multiple system atrophy (MSA), a less common rare neurodegenerative disease with widespread effects on the brain and body, α-syn accumulates as glial cytoplasmic inclusions (GCI) outside the nucleus in the cytoplasm in brain structural cells.
Researchers found that GCIs are more compact and potent in causing neurodegeneration compared to Lewy body disorders, which is why MSA is far more aggressive. The difference in the diseases lies within the cell environment and that dictates what form the misfolded α-syn becomes.
This study reveals the effect of not just protein pathology, but the cellular environment itself, on the development of disease. According to Chao Peng, a researcher at the Center for Neurodegenerative Disease Research and first author on the paper, “These unexpected findings of the effect of cell type on the generation of different α-syn strains addresses one of the most important mysteries in neurodegenerative disease research.”
Read more about the study at Penn Medicine News.