PERICYTES AS CONVERGING TARGETS OF GENETIC RISK AND ENVIRONMENTAL EXPOSURE IN PARKINSON’S DISEASE

Pericytes are critical regulators of blood-brain barrier (BBB) integrity and neuroinflammatory signaling, yet their contribution to neurodegenerative disease pathology remains insufficiently characterized. BBB dysfunction and chronic neuroinflammation are prominent features of Parkinson’s disease (PD), suggesting that pericyte dysfunction may play a previously underappreciated role in disease progression. In parallel, emerging evidence indicates that environmental nanoplastics may exacerbate PD-related pathology by promoting α-synuclein (aSyn) aggregation and compromising BBB function.

In this study, we investigated pericyte involvement in PD using human induced pluripotent stem cell-derived pericyte-like cells generated from healthy controls and PD patients carrying the LRRK2 G2019S mutation. Cells were exposed to aSyn, polystyrene nanoplastics with different surface charges, and the pro-inflammatory cytokine interleukin-1β to assess effects on pericyte function, inflammatory responses, and nanoparticle uptake.

We demonstrate that the LRRK2 G2019S mutation significantly impairs pericyte-like cell migration and alters the release of inflammatory mediators. Preliminary data further indicate that anionic polystyrene nanoplastics are taken up more readily and form larger intracellular aggregates than cationic or neutral nanoplastics. However, short-term co-exposure to aSyn and anionic nanoplastics did not increase intracellular aSyn levels compared with aSyn exposure alone.

Together, these findings support a role for pericytes in PD-related inflammatory and potentially vascular dysfunction. While pericyte-like cells efficiently internalize nanoplastics, their long-term impact on pericyte function and contribution to PD pathology require further investigation. This work highlights pericytes as a relevant cellular target at the interface of genetic susceptibility, neuroinflammation, and environmental risk factors in PD.