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New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases

1
Faculty of Sciences, Universidad de Chile, Las Palmeras 3425, Santiago 7800024, Chile
2
Center for the Treatment of Movement Disorders, Universidad de Santiago de Chile, Belisario Prat 1597, Santiago 83800000, Chile
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2018, 11(4), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040109
Received: 25 June 2018 / Revised: 31 July 2018 / Accepted: 3 August 2018 / Published: 19 October 2018
(This article belongs to the Special Issue Iron as Therapeutic Targets in Human Diseases)
Iron chelation has been introduced as a new therapeutic concept for the treatment of neurodegenerative diseases with features of iron overload. At difference with iron chelators used in systemic diseases, effective chelators for the treatment of neurodegenerative diseases must cross the blood–brain barrier. Given the promissory but still inconclusive results obtained in clinical trials of iron chelation therapy, it is reasonable to postulate that new compounds with properties that extend beyond chelation should significantly improve these results. Desirable properties of a new generation of chelators include mitochondrial destination, the center of iron-reactive oxygen species interaction, and the ability to quench free radicals produced by the Fenton reaction. In addition, these chelators should have moderate iron binding affinity, sufficient to chelate excessive increments of the labile iron pool, estimated in the micromolar range, but not high enough to disrupt physiological iron homeostasis. Moreover, candidate chelators should have selectivity for the targeted neuronal type, to lessen unwanted secondary effects during long-term treatment. Here, on the basis of a number of clinical trials, we discuss critically the current situation of iron chelation therapy for the treatment of neurodegenerative diseases with an iron accumulation component. The list includes Parkinson’s disease, Friedreich’s ataxia, pantothenate kinase-associated neurodegeneration, Huntington disease and Alzheimer’s disease. We also review the upsurge of new multifunctional iron chelators that in the future may replace the conventional types as therapeutic agents for the treatment of neurodegenerative diseases. View Full-Text
Keywords: neurodegeneration with brain iron accumulation; iron chelation therapy; multifunctional iron chelators neurodegeneration with brain iron accumulation; iron chelation therapy; multifunctional iron chelators
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MDPI and ACS Style

Nuñez, M.T.; Chana-Cuevas, P. New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases. Pharmaceuticals 2018, 11, 109. https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040109

AMA Style

Nuñez MT, Chana-Cuevas P. New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases. Pharmaceuticals. 2018; 11(4):109. https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040109

Chicago/Turabian Style

Nuñez, Marco T., and Pedro Chana-Cuevas. 2018. "New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases" Pharmaceuticals 11, no. 4: 109. https://0-doi-org.brum.beds.ac.uk/10.3390/ph11040109

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