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LRRK2 G2019S variant triggers transcriptional changes in Parkinson’s disease human myeloid cells under pro-inflammatory environment

ABSTRACT: The G2019S mutation in the LRRk2 gene is a major Parkinson’s disease risk factor. We studied its effect on microglial activity and found that it remains inactive under normal conditions but strongly affects gene regulation when exposed to inflammation such as LPS and IFNg. The mutation increases lipid metabolism and phagolysosomal genes in microglia, enhancing their ability to clear myelin debris. It also disrupts cell cycle genes, decreasing proliferation and E2F4 regular.These findings reveal G2019S’s significant impact on myeloid cell gene activity during inflammation, highlighting lipid imbalance as a key factor in functional disruptions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE240907 | GEO | 2023/09/30

REPOSITORIES: GEO

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