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Pericytes: a link between Parkinson-related protein and blood-brain barrier disruption?

Portrait photo of Gesine Paul Visse
Gesine Paul-Visse, Associate Professor and last author of the study.

Overexpression of the Parkinson-related protein, α-synuclein, leads to blood-brain barrier leakage and pericyte activation in mice. A study published in Scientific Reports identifies pericytes as potential target cells for early interventions.

Parkinson’s disease is a movement disorder caused by the accumulation and aggregation of α-synuclein and degeneration of dopaminergic neurons. Disruption of the blood-brain barrier and other microvascular alterations are increasingly recognized as a common denominator of several neurodegenerative disorders. To develop new therapies, it is essential to understand the underlying pathological processes that might aggravate the neurodegeneration.

Pericytes are uniquely positioned at the blood-brain interface. These cells maintain vascular function. Microvascular changes often involve pathological pericyte activation and bloodbrain barrier dysfunction. This creates a hostile microenvironment which may contribute to disease progression. Increasing knowledge about these mechanisms could unravel possible targets for early treatments and protection of the blood-brain barrier.

Gesine Paul-Visse and Jia-Yi Li are both research leaders in Multipark. Jia-Yi Li has developed a mouse model overexpressing human α-synuclein, a protein that is pathologically aggregating in Parkinson’s disease. Gesine Paul-Visse has a long experience in studying pericyte function. In collaboration, they investigated how a progressive accumulation of α-synuclein affects these cells and brain vasculature over time. 

- Interestingly, changes such as pericyte activation and blood-brain-barrier leakage are already observed at the early stages of the disorder, even before behavioral changes or dopaminergic cell loss can be detected, explains Gesine Paul-Visse.

Endothelial cells build up the vessel wall and control the exchange between the blood and surrounding brain tissue. Previous cell culture studies indicate that α-synuclein requires the presence of pericytes to induce hyperpermeability in endothelial cells. Hence, it is possible that the dysregulation of the blood-brain barrier induced by α-synuclein depends on pericytes also in the brain.

The next step would be to investigate which proteins are secreted from pericytes and endothelial cells in α-synuclein mouse models. Addressing this could point to new avenues for therapeutic approaches targeting the neurovascular unit in Parkinson’s disease

Read more about theis study in Scientific Reports

Confocal images illustrating extravascular fibrinogen