The transition metals copper and iron in neurodegenerative diseases.
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.
Rivera-Mancía
Susana
S
Neurochemistry Department, National Institute of Neurology and Neurosurgery Manuel Velasco Suárez, Mexico City, Mexico.
Pérez-Neri
Iván
I
Ríos
Camilo
C
Tristán-López
Luis
L
Rivera-Espinosa
Liliana
L
Montes
Sergio
S
D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002614:Chelating Agents / Q000627:therapeutic use; D003300:Copper / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism
D002352:Carrier Proteins; D002614:Chelating Agents; D003300:Copper; D007501:Iron