Iron Pathophysiology in Parkinson Diseases

The key molecular events that provoke Parkinson's disease (PD) are not fully understood. Iron deposit was found in the substantia nigra pars compacta (SNpc) of PD patients and animal models, where dopaminergic neurons degeneration occurred selectively. The mechanisms involved in disturbed iron metabolism remain unknown, however, considerable evidence indicates that iron transporters dysregulation, activation of L-type voltage-gated calcium channel (LTCC) and ATP-sensitive potassium (KATP) channels, as well as N-methyl-D-aspartate (NMDA) receptors (NMDARs) contribute to this process. There is emerging evidence on the structural links and functional modulations between iron and α-synuclein, and the key player in PD which aggregates in Lewy bodies. Iron is believed to modulate α-synuclein synthesis, post-translational modification, and aggregation. Furthermore, glia, especially activated astroglia and microglia, are involved in iron deposit in PD. Glial contributions were largely dependent on the factors they released, e.g., neurotrophic factors, pro-inflammatory factors, lactoferrin, and those undetermined. Therefore, iron chelation using iron chelators, the extracts from many natural foods with iron chelating properties, may be an effective therapy for prevention and treatment of the disease.