Iron as a therapeutic target for Parkinson's disease

An urgent need for efficacious disease modifying therapies is required to slow downParkinson’s disease (PD) progression. Iron is required as a cofactor in metabolic processesthroughout the body and specifically in tissues of high oxygen consumption, such as thecentral nervous system. The redox chemistry of iron is critical for neurotransmitter regulationas well as mitochondrial oxidative phosphorylation, nitric oxide metabolism and oxygentransport.1 Iron homeostasis involves the orchestration of systemic and cellular networks forthe acquisition, internal distribution and utilization of iron.2 Disruption of links can lead toabnormal redistribution of iron, causing deleterious consequences (siderosis) either bylocalized accumulation and/or deficits in specific cellular compartments or tissues. Excessivelabile iron in the substantia nigra pars compacta (SNc) has become a pathognomonic hallmarkof PD and leads to increased production of noxious reactive oxygen species (ROS), which isalso prevalent in PD. Conversely, a deficiency in iron impairs energy production2 and can alsocause dopaminergic neurodegeneration in mice.3 In mammalian models, chelators thatscavenge intracellular iron protect against oxidative neuronal damage. However, these strongiron chelation regimens are designed to treat systemic siderosis and are not suitable for PDpatients, as iatrogenic iron depletion and anaemia may ensue. Moderate iron chelationmodality that conserves systemic iron offers a novel therapeutic strategy for neuroprotection