CONICET | Buscador de Institutos y Recursos Humanos

Abstract. The importance of oxidative damage to the pathogenesis of many neurodegenerative processes has become increasingly apparent over the past few years. Furthermore, it has been suggested that iron-induced oxidative stress can play a key role in the pathogenesis of several neurodegenerative diseases. Iron progressively accumulates in the brain both during normal aging and neurodegenerative processes. However, iron accumulation occurs without the concomitant increase in tissue ferritin, which could increase the risk of oxidative stress. Moreover, 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-mediated increase in cell oxidants on 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 lipid signaling and oxidative stress in the development of neurodegeneratives diseases. In this article, we will review the role of phosphatidylinositol 3-kinase/Akt, phosphatidylcholinespecific phospholipase C, phospholipase D and phospholipase A2 pathways in signaling events triggered by iron neurotoxicity.

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