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It can transactivate ferritin in response to ferroptosis triggers and inflammation, and by regulating p21, it can bolster the antioxidative defenses of the brain, particularly by inhibiting glutathione degradation and enhancing GPX4 activity [67]

BrulsYMde LigtMLindeboomLPhielixEHavekesBSchaartGet al

In summary, CDC42, derived from neural stem cell-derived exosomes, as well as TIGAR, FTO, and IRP2, contribute to PD pathology by regulating iron homeostasis, ferroptosis, fatty acid metabolism, the antioxidant system, and angiogenesis

In acute myeloid leukemia cells, reduced MTHFR function, whether due to polymorphisms or pharmacologic inhibition, decreases intracellular SAM, leading to loss of the repressive histone marks H3K27me3 and H3K9me3 and de-repression of transcription factors such as SPI1 (85)

As multi-ethnic, longitudinal cohorts expand, these composite biomarker panels are expected to define individual risk trajectories, differentiate PD subtypes, and identify windows of therapeutic opportunity before irreversible neurodegeneration sets in