Brain Iron Metabolism Dysfunction in Parkinson's Disease

Dysfunction of iron metabolism, which includes its uptake, storage, and release, plays a key role in neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease, and Huntington's disease. Understanding how iron accumulates in the substantia nigra (SN) and why it specifically targets dopaminergic (DAergic) neurons is particularly warranted for PD, as this knowledge may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for this disease. In this review, we begin with a brief introduction describing brain iron metabolism and its regulation. We then provide a detailed description of how iron accumulates specifically in the SN and why DAergic neurons are especially vulnerable to iron in PD. Furthermore, we focus on the possible mechanisms involved in iron-induced cell death of DAergic neurons in the SN. Finally, we present evidence in support that iron chelation represents a plausable therapeutic strategy for PD.