Metal based neurodegenerative diseases - From molecular mechanisms to therapeutic strategies

Crichton, Robert;Dexter, D. T.;Ward, Roberta J.
(2008) Coordination Chemistry Reviews — Vol. 252, n° 10-11, p. 1189-1199 (2008)

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Authors
  • Crichton, RobertUCLouvain
    Author
  • Dexter, D. T.
    Author
  • Ward, Roberta J.UCLouvain
    Author
Abstract
The hypothesis is presented that changes in metal ion homeostatic control, particularly of redox-active metals such as iron and copper, in specific brain regions, leads to the generation of reactive oxygen species, which either directly damage key proteins, or lead to the formation of reactive aldehydes. These, in turn, generate protein carbonyls, leading to protein denaturation, aggregation, and a failure of the ubiquitin/proteasome system to eliminate these defective proteins. We present the evidence for metal based neurodegeneration in Parkinson's and Alzheimer's disease. Possible therapeutic strategies are presented which could remove such excesses of these specific metals and lead to the diminishment of the neurodegenerative processes. (C) 2007 Elsevier B.V. All rights reserved.
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Crichton, R., Dexter, D. T., & Ward, R. J. (2008). Metal based neurodegenerative diseases - From molecular mechanisms to therapeutic strategies. Coordination Chemistry Reviews, 252(10-11), 1189-1199. https://doi.org/10.1016/j.ccr.2007.10.019 (Original work published 2008)