The role of iron and copper in the aetiology of neurodegenerative disorders: therapeutic implications.
Abnormalities in the metabolism of the transition metals iron and copper have been demonstrated to play a crucial role in the pathogenesis of various neurodegenerative diseases. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed in this article in depth. While there is documented evidence for alterations in the homeostasis, redox-activity and localisation of transition metals, it is also important to realise that alterations in specific copper- and iron-containing metalloenzymes appear to play a crucial role in the neurodegenerative process. These changes provide the opportunity to identify pathways where modification of the disease process can occur, potentially offering opportunities for clinical intervention. As understanding of disease aetiology evolves, so do the tools with which diseases are treated. In this article, we examine not only the possible mechanism of disease but also how pharmaceuticals may intervene, from direct and indirect antioxidant therapy to strategies involving gene therapy.
Perry
George
G
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. gxp@po.cwru.edu
Sayre
Lawrence M
LM
Atwood
Craig S
CS
Castellani
Rudolph J
RJ
Cash
Adam D
AD
Rottkamp
Catherine A
CA
Smith
Mark A
MA
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000975:Antioxidants / Q000627:therapeutic use; D002614:Chelating Agents / Q000627:therapeutic use; D003300:Copper / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D017096:Prion Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D000975:Antioxidants; D002614:Chelating Agents; D005609:Free Radicals; D003300:Copper; D007501:Iron