Human iPSC-derived pericyte-like cells carrying the LRRK2 mutation induce a reactive phenotype and alter migration

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Abstract BACKGROUND Pericytes play a crucial role in controlling inflammation and vascular functions in the central nervous system, which are impaired in Parkinson’s disease. Still, there is a lack of studies on the impact of pericytes on neurodegenerative diseases, and their involvement in the pathology of Parkinson’s disease is unclear. Our objective was to investigate the molecular and functional differences between healthy pericytes and pericytes harboring the LRRK2 G2019S mutation, a prevalent mutation linked to Parkinson’s disease. METHODS This study utilized pericyte-like cells derived from induced pluripotent stem cells obtained from Parkinson’s disease patients with the LRRK2 G2019S mutation and healthy individuals. We examined the gene expression profiles of these cells and assessed how the modifications impact their functionality. RESULTS We have demonstrated differences in the expression of genes related to inflammation and angiogenesis. Furthermore, we have observed that proinflammatory stimuli modify migration speed in Parkinson’s disease pericyte-like cells and enhance the secretion of inflammatory mediators, such as soluble VCAM-1 and MCP-1. CONCLUSIONS In summary, our findings support the notion that pericytes play a role in the inflammatory and vascular changes observed in Parkinson’s disease. Further investigation of pericytes could provide valuable insight into the pathophysiology of Parkinson’s disease.

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