The relevance of metals in the pathophysiology of neurodegeneration, pathological considerations.

Neurodegenerative disorders are featured by a variety of pathological conditions that share similar critical processes, such as oxidative stress, free radical activity, proteinaceous aggregations, mitochondrial dysfunctions, and energy failure. They are mediated or triggered by an imbalance of metal ions leading to changes of critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. Their causes are multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper, and other trace metals. They are present at elevated levels in Alzheimer disease, Parkinson disease, multisystem atrophy, etc., while in other neurodegenerative disorders, copper, zinc, aluminum, and manganese are involved. This chapter will review the recent advances of the role of metals in the pathogenesis and pathophysiology of major neurodegenerative diseases and discuss the use of chelating agents as potential therapies for metal-related disorders.