Iron as a therapeutic target for Parkinson's disease - Université de Lille
Article Dans Une Revue Movement Disorders Année : 2018

Iron as a therapeutic target for Parkinson's disease

James A. Duce
  • Fonction : Auteur
Olivier Rascol
Daniela Berg
  • Fonction : Auteur
David Dexter
  • Fonction : Auteur
Z. Ioav Cabantchik
  • Fonction : Auteur
Ashley I. Bush
  • Fonction : Auteur

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.
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Dates et versions

hal-02150661 , version 1 (07-06-2019)

Identifiants

Citer

Caroline Moreau, James A. Duce, Olivier Rascol, Jean Christophe Devedjan, Daniela Berg, et al.. Iron as a therapeutic target for Parkinson's disease. Movement Disorders, 2018, Movement Disorders, 33 (4), pp.568-574. ⟨10.1002/mds.27275⟩. ⟨hal-02150661⟩

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