Iron and mechanisms of neurotoxicity

SALVADOR GABRIELA AUTOR CORRESP.; URANGA ROMINA; GIUSTO, NORMA

International Journal of Alzheimer Disease

Jindawi

Lugar: Oxford; Año: 2011 vol. 1 p. 1 - 7

2090-0252

The accumulation of transition metals (e.g. copper, zinc, iron) and the dysregulation of their metabolism are a hallmark in the pathogenesis of several neurodegenerative diseases. This review will be focused on the mechanism of neurotoxicity mediated by iron. This metal progressively accumulates in the brain both during normal aging and neurodegenerative processes. However, iron accumulation occurs without the concomitant increase in tissue ferritin, which may increase the risk of oxidative stress. High iron concentrations in the brain have been consistently observed in Alzheimer´s (AD) and Parkinson´s (PD) diseases. In this connection, metalloneurobiology has become extremely important in establishing the role of iron in the onset and progression of neurodegenerative diseases. Neurons have developed several protective mechanisms against oxidative stress, among them, the activation of cellular signaling pathways. The final response will depend on the identity, intensity and persistence of the oxidative insult. The characterization of the mechanisms mediating the effects of iron-induced increase in neuronal dysfunction and death is central to understanding the pathology of a number of neurodegenerative disorders. Accumulating evidence points toward a potentially important link between abnormal or deregulated iron metabolism and, consequently, oxidative stress as one of the main contributors to the development of neurodegenerative diseases.