BNA 2023 | Extracellular vesicles in Parkinson’s disease
Tiago Outeiro, PhD, University Medical Center Göttingen, Göttingen, Germany, discusses the growing interest in extracellular vesicles (ECVs) as a research and clinical tool in Parkinson’s disease. ECVs containing diverse contents are released from cells and thus participate in a plethora of biological processes. Key functions include waste removal and facilitating cell-to-cell communication by delivering cargo to recipient cells. It has been suggested that ECVs in the central nervous system could play a role in Parkinson’s disease through the transport of alpha synuclein. Studying the cargo, mechanisms of release, and impacts of cell-to-cell communication on recipient cells could shed light on disease pathophysiology, as well as identifying potential biomarkers and intervention targets. Prof. Outeiro outlines his work looking into the release of different proteins implicated in neurodegenerative diseases and their onward journeys. This interview took place at The BNA 2023 International Festival of Neuroscience in Brighton, UK.
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Transcript (edited for clarity)
So the role of extracellular vesicles in Parkinson’s disease is a concept that is emerging and not just in Parkinson’s but in other neurodegenerative diseases as well. And it’s in a way a bit imported from cancer. So extracellular vesicles are these small vesicles, as the name implies, that are released by cells. Cells release a variety of cargoes, different molecules that can be sent to the outside environment as a means for sending signals to other cells or for cells to getting rid of molecules that they don’t want to keep inside...
So the role of extracellular vesicles in Parkinson’s disease is a concept that is emerging and not just in Parkinson’s but in other neurodegenerative diseases as well. And it’s in a way a bit imported from cancer. So extracellular vesicles are these small vesicles, as the name implies, that are released by cells. Cells release a variety of cargoes, different molecules that can be sent to the outside environment as a means for sending signals to other cells or for cells to getting rid of molecules that they don’t want to keep inside.
in the context of Parkinson’s, we approach this because we thought that this could be one route for cells to release alpha-synuclein. The protein that is accumulating in the pathological inclusions found in the brains of patients. And we thought this would be a way for cells to get rid of alpha-synuclein that they don’t want anymore because maybe it’s aggregated, maybe it’s causing problems or also as part of a physiological process that requires the cells to send alpha-synuclein to the outside. And that’s what I’ll be focusing on here at the BNA and I’ll talk about this from our efforts to understand the biology of release of these vesicles, we compared actually the release of different proteins inside these vesicles. So alpha-synuclein, tau, which is associated with Alzheimer’s disease, and huntingtin which is involved in Huntington’s disease. And we found some differences in the way cells release these proteins and also some similarities. And we asked whether these extracellular vesicles would then be able to send the proteins to other cells, neurons, microglia. And we tried to understand what were some of the effects for those cells when they receive these molecules from extracellular vesicles. And so this has implications both in terms of potential targets for therapeutic intervention but also as biomarkers. We are living now exciting times. When a recent study was published with the largest number of patients enrolled in the study where they used the seeding amplification assay to measure the ability of alpha-synuclein to seed non-aggregated protein and these extracellular vesicles could contain also seed competent species of alpha-synuclein that could be involved in the spreading of pathology.
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