Iron mishandling in the brain and periphery in Parkinson's disease

The heterogeneous prodromal phase of Parkinson's disease (PD) has made identifying catalysts that drive disease progression critical for effective development of disease-modifying therapies. Recently, the role of gastrointestinal dysfunction in inflammation that drives neurodegenerative risk has gained attention as a target for intervention. However, to date, there have been no clear internal or environmental catalysts identified in the gut that drive risk for PD. Here, we review the literature on iron dysregulation in the brain, blood, and gut in PD and propose that iron dysregulation outside the brain is an important catalyst that may represent a prodromal mechanistic link in gut-first PD.