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Fluids and Barriers of the CNS
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Open Access 01-12-2024 | Parkinson Disease | Research

Mutated LRRK2 induces a reactive phenotype and alters migration in human iPSC-derived pericyte-like cells

Authors: Sanni Peltonen, Tuuli-Maria Sonninen, Jonna Niskanen, Jari Koistinaho, Marika Ruponen, Šárka Lehtonen

Published in: Fluids and Barriers of the CNS | Issue 1/2024

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Abstract

Background

Pericytes play a crucial role in controlling inflammation and vascular functions in the central nervous system, which are disrupted in Parkinson’s disease (PD). Still, there is a lack of studies on the impact of pericytes on neurodegenerative diseases, and their involvement in the pathology of PD is unclear. Our objective was to investigate the molecular and functional differences between healthy pericytes and pericytes with the LRRK2 G2019S mutation, which is one of the most common mutations associated with PD.

Methods

Our study employed pericyte-like cells obtained from induced pluripotent stem cells produced from PD patients with the LRRK2 G2019S mutation as well as from healthy individuals. We examined the gene expression profiles of the cells and analyzed how the alterations reflect on their functionality.

Results

We have shown differences in the expression of genes related to inflammation and angiogenesis. Furthermore, we observe modified migration speed in PD pericyte-like cells as well as enhanced secretion of inflammatory mediators, such as soluble VCAM-1 and MCP-1, in these pericyte-like cells following exposure to proinflammatory stimuli.

Conclusions

In summary, our findings support the notion that pericytes play a role in the inflammatory and vascular changes observed in PD. Further investigation of pericytes could provide valuable insight into understanding the pathogenesis of PD.
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Metadata
Title
Mutated LRRK2 induces a reactive phenotype and alters migration in human iPSC-derived pericyte-like cells
Authors
Sanni Peltonen
Tuuli-Maria Sonninen
Jonna Niskanen
Jari Koistinaho
Marika Ruponen
Šárka Lehtonen
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2024
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-024-00592-y

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