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Oxidative stress and neurodegeneration: the involvement of iron

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Abstract

Many evidences indicate that oxidative stress plays a significant role in a variety of human disease states, including neurodegenerative diseases. Iron is an essential metal for almost all living organisms due to its involvement in a large number of iron-containing proteins and enzymes, though it could be also toxic. Actually, free iron excess generates oxidative stress, particularly in brain, where anti-oxidative defences are relatively low. Its accumulation in specific regions is associated with pathogenesis in a variety of neurodegenerative diseases (i.e., Parkinson’s disease, Alzheimer’s disease, Huntington’s chorea, Amyotrophic Lateral Sclerosis and Neurodegeneration with Brain Iron Accumulation). Anyway, the extent of toxicity is dictated, in part, by the localization of the iron complex within the cell (cytosolic, lysosomal and mitochondrial), its biochemical form, i.e., ferritin or hemosiderin, as well as the ability of the cell to prevent the generation and propagation of free radical by the wide range of antioxidants and cytoprotective enzymes in the cell. Particularly, ferrous iron can act as a catalyst in the Fenton reaction that potentiates oxygen toxicity by generating a wide range of free radical species, including hydroxyl radicals (·OH). The observation that patients with neurodegenerative diseases show a dramatic increase in their brain iron content, correlated with the production of reactive oxigen species in these areas of the brain, conceivably suggests that disturbances in brain iron homeostasis may contribute to the pathogenesis of these disorders. The aim of this review is to describe the chemical features of iron in human beings and iron induced toxicity in neurodegenerative diseases. Furthermore, the attention is focused on metal chelating drugs therapeutic strategies.

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Acknowledgements

The authors gratefully acknowledge the financial support provided by Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR, Italy).

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  1. Alessia Carocci and Alessia Catalano have equally contributed to this work.

Authors and Affiliations

  1. Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari “A. Moro”, 70125, Bari, Italy

    Alessia Carocci & Alessia Catalano

  2. Dipartimento di Farmacia e Scienze della Salute e della Nutrizione, Università della Calabria, 87036, Arcavacata Di Rende (Cosenza), Italy

    Maria Stefania Sinicropi & Giuseppe Genchi

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  1. Alessia Carocci
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  2. Alessia Catalano
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  3. Maria Stefania Sinicropi
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Correspondence to Maria Stefania Sinicropi.

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Carocci, A., Catalano, A., Sinicropi, M.S. et al. Oxidative stress and neurodegeneration: the involvement of iron. Biometals 31, 715–735 (2018). https://doi.org/10.1007/s10534-018-0126-2

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