Iron as a therapeutic target for Parkinson's disease
Résumé
An urgent need for efficacious disease modifying therapies is required to slow down
Parkinson’s disease (PD) progression. Iron is required as a cofactor in metabolic processes
throughout the body and specifically in tissues of high oxygen consumption, such as the
central nervous system. The redox chemistry of iron is critical for neurotransmitter regulation
as well as mitochondrial oxidative phosphorylation, nitric oxide metabolism and oxygen
transport.1 Iron homeostasis involves the orchestration of systemic and cellular networks for
the acquisition, internal distribution and utilization of iron.2 Disruption of links can lead to
abnormal redistribution of iron, causing deleterious consequences (siderosis) either by
localized accumulation and/or deficits in specific cellular compartments or tissues. Excessive
labile iron in the substantia nigra pars compacta (SNc) has become a pathognomonic hallmark
of PD and leads to increased production of noxious reactive oxygen species (ROS), which is
also prevalent in PD. Conversely, a deficiency in iron impairs energy production2 and can also
cause dopaminergic neurodegeneration in mice.3 In mammalian models, chelators that
scavenge intracellular iron protect against oxidative neuronal damage. However, these strong
iron chelation regimens are designed to treat systemic siderosis and are not suitable for PD
patients, as iatrogenic iron depletion and anaemia may ensue. Moderate iron chelation
modality that conserves systemic iron offers a novel therapeutic strategy for neuroprotection.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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