What is it about?
Parkinson’s disease is usually linked to the loss of dopamine-producing neurons, but our study shows that another type of brain cell, called astrocytes, may play a much more active role than previously thought. Using stem cells from patients with a genetic form of Parkinson’s, we recreated interactions between human neurons and astrocytes in the lab. We found that astrocytes carrying the p.A53T mutation in α-synuclein fail to keep protein balance and cannot clear toxic protein aggregates effectively. As a result, harmful aggregates form and neurons become more vulnerable. Healthy astrocytes, however, can partially rescue these problems.
Featured Image
Photo by Bioscience Image Library by Fayette Reynolds on Unsplash
Why is it important?
These findings show that astrocytes are not just passive supporters of neurons but can actively drive Parkinson’s-related damage. Understanding their role opens the door to new therapeutic strategies that target astrocyte dysfunction, improve protein clearance, or prevent α-synuclein buildup. It also provides a powerful human stem-cell–based model for developing and testing future treatments.
Perspectives
This work suggests several future directions. Researchers can now investigate which specific astrocyte pathways trigger neuronal damage and explore drugs that restore healthy proteostasis or calcium handling. The stem-cell coculture model can also be used to test personalized therapies based on patient-derived cells. Ultimately, uncovering how astrocytes contribute to Parkinson’s disease may help shift the focus of therapy development toward the wider cellular environment, not just neurons.
FLORENTIA PAPASTEFANAKI
Hellenic Pasteur Institute
Read the Original
This page is a summary of: Dysregulated proteostasis in p.A53T-α-Synuclein astrocytes aggravates Lewy-like neuropathology in a Parkinson’s disease iPSC model, Proceedings of the National Academy of Sciences, November 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2505240122.
You can read the full text:
Contributors
The following have contributed to this page
