Ferritin iron uptake and release in the presence of metals and metalloproteins: Chemical implications in the brain

• The available information of ferritin iron uptake and release is reviewed.
• The influence of metals and metalloproteins in these processes has been discussed.
• The chemical implications have been analyzed.
• The relationship with some neuropathologies has been drawn.

Living organisms have developed a chemical machinery based on the ferritin protein for the storage, under a nontoxic form, of the iron that is not required for immediate metabolic purposes. Whereas free iron causes extensive cell damage, ferritin iron is not toxic, yet still available for cell requirements. However, iron storage in ferritin is increasingly being recognized as a crucial process related with some neurodegenerative disorders and therefore, an understanding of the management of iron in the brain, especially the processes of iron uptake and release in ferritin, is compulsory to clarify the role of this metalloprotein in these neuropathologies.Although knowledge of iron storage and iron release in ferritin is nowadays still limited, even less information is currently available about the influence of free metal ions and other brain metalloproteins in these processes.In this sense, this review is an excellent opportunity to collect all the information today available about the influence of metals and metalloproteins in ferritin loading and unloading events, which until now are dispersed in the literature. Furthermore, we will focus on the importance of all the above-mentioned interactions in the brain, since the importance of the correct and safe balance of metals in the brain after their well-known implication in neurodegenerative processes such as the Alzheimer's (AD), Parkinson (PD) and prion protein (PPD) diseases is obvious. In this work, we will not only recall the importance and role of ferritin in the brain but also the putative influence of the interaction between ferritin and some metals and/or metalloproteins and other biomolecules on these neurological dysfunctions. The final part of the review will be devoted to draw some guidelines to where the future prospects point to on the basis of the existing information.