NeuroMolecular Medicine

, Volume 11, Issue 4, pp 223–238 | Cite as

Metal Ion Physiopathology in Neurodegenerative Disorders

  • Silvia Bolognin
  • Luigi Messori
  • Paolo ZattaEmail author
Review Paper


Metal dyshomeostasis in the brain (BMD) has often been proposed as a possible cause for several neurodegenerative disorders (NDs). Nevertheless, the precise nature of the biochemical mechanisms of metal involvement in NDs is still largely unknown. Mounting evidence suggests that normal aging itself is characterized by, among other features, a significant degree of metal ion dysmetabolism in the brain. This is probably the result of a progressive deterioration of the metal regulatory systems and, at least in some cases, of life-long metal exposure and brain accumulation. Although alterations of metal metabolism do occur to some extent in normal aging, they appear to be highly enhanced under various neuropathological conditions, causing increased oxidative stress and favoring abnormal metal–protein interactions. Intriguingly, despite the fact that most common NDs have a distinct etiological basis, they share striking similarities as they are all characterized by a documented brain metal impairment. This review will primarily focus on the alterations of metal homeostasis that are observed in normal aging and in Alzheimer’s disease. We also present a brief survey on BMD in other NDs (Amyotrophic Lateral Sclerosis, Parkinson’s, and Prion Protein disease) in order to highlight what represents the most reliable evidence supporting a crucial involvement of metals in neurodegeneration. The opportunities for metal-targeted pharmacological strategies in the major NDs are briefly outlined as well.


Alzheimer’s disease Metal ions Aluminum Neurological disorders Chelation therapy 



This work was supported by Grants from CNR/MIUR (FIRB No. RBNE03PX83) and PRIN 2007.


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© Humana Press Inc. 2009

Authors and Affiliations

  1. 1.CNR-Institute for Biomedical Technologies, Padua “Metalloproteins” Unit, Department of BiologyUniversity of PaduaPaduaItaly
  2. 2.Laboratory of Metals in Medicine “METMED”, Department of ChemistryUniversity of FlorenceSesto Fiorentino, FlorenceItaly

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