Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration. Toxics 2014

Abstract
As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper deficiency are associated with brain dysfunction. The redox capacities of free copper, its ability to trigger the production of reactive oxygen species and the close relationships with the regulation of iron and zinc are remarkable features. Major advances in our understanding of the relationships between copper, neuronal functions and neurodegeneration have occurred these last two decades. The metabolism of copper and the current knowledge on the consequences of copper dysregulation on brain disorders are reviewed, with a focus on neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease and Parkinson’s disease. In vitro studies, in vivo experiments and evidence from clinical observations of the neurotoxic effects of copper provide the basis for future therapies targeting copper homeostasis.

“...Conclusions
Copper is an essential transition metal. It participates in critical cuproenzymes preventing neurodegeneration and regulating neurotransmission. Via the ferroxidase activity of ceruloplasmin, copper is a metabolic regulator of the contents of iron in the CNS. An excess of free copper is directly involved to neurodegeneration. WD, AD and PD are major neurodegenerative disorders associated with copper dyshomeostasis. Acting on copper metabolism represents a therapeutic approach for these severe disorders of the CNS. Gene therapy, gene induction, metal modulators promoting the redistribution between compartments and administration of ceruloplasmin are promising possibilities that deserve specific studies.”

full paper: http://www.mdpi.com/2305-6304/2/2/327/htm