The transition metals copper and iron in neurodegenerative diseases,

abstract

Neurodegenerative diseases constitute a worldwide health problem. Metals like iron and copper are essential for life, but they are also involved in several neurodegenerative mechanisms such as protein aggregation, free radical generation and oxidative stress. The role of Fe and Cu, their pathogenic mechanisms and possible therapeutic relevance are discussed regarding four of the most common neurodegenerative diseases, Alzheimer’s, Parkinson’s and Huntington’s diseases as well as amyotrophic lateral sclerosis. Metal-mediated oxidation by Fenton chemistry is a common feature for all those disorders and takes part of a self-amplifying damaging mechanism, leading to neurodegeneration. The interaction between metals and proteins in the nervous system seems to be a crucial factor for the development or absence of neurodegeneration. The present review also deals with the therapeutic strategies tested, mainly using metal chelating drugs. Metal accumulation within the nervous system observed in those diseases could be the result of compensatory mechanisms to improve metal availability for physiological processes.

"... Conclusions: All of the evidence discussed above suggests that disturbances of metal functioning, regulation and distribution are likely to occur. Mechanisms of damage elicited by Cu and Fe common to AD, PD, ALS and HD include: (a) free radical production, (b) protein aggregation and (c) metal transport alteration. Although there are some studies regarding the role of metal transporters (Table 1) in neurodegenenerative diseases, this is a growing study field, having the possibility of studying novel therapeutic strategies, since metal transporters are involved in brain metal distribution, intracellular localization as well as disposal from brain. It is possible that the final pictures of metal status in neurodegenerative diseases obeys to altered compartamentalization of metals and thus we observe the sum of disturbances caused by the disease and by tissue compensative actions. Detailed studies on the links between altered metal transport and neurodegeneration will be helpful to facilitate the search for effective therapeutic strategies to avoid damage caused by metal dyshomeostasis..."
source: http://www.sciencedirect.com/science/article/pii/S0009279710002711?via%3Dihub