New Perspectives in Iron Chelation Therapy for the Treatment of Neurodegenerative Diseases.
Nuñez MT1, Chana-Cuevas P2.
Pharmaceuticals (Basel). 2018 Oct 19;11(4). pii: E109.
doi: 10.3390/ph11040109.

Abstract
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.

KEYWORDS:
iron chelation therapy; multifunctional iron chelators; neurodegeneration with brain iron accumulation

PMID: 30347635 DOI: 10.3390/ph11040109

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