Copper transport and Alzheimer's disease.
This brief review discusses copper transport in humans, with an emphasis on knowledge learned from one of the simplest model organisms, yeast. There is a further focus on copper transport in Alzheimer's Disease (AD). Copper homeostasis is essential for the well-being of all organisms, from bacteria to yeast to humans: survival depends on maintaining the required supply of copper for the many enzymes, dependent on copper for activity, while ensuring that there is no excess free copper, which would cause toxicity. A virtual orchestra of proteins are required to achieve copper homeostasis. For copper uptake, Cu(II) is first reduced to Cu(I) via a membrane-bound reductase. The reduced copper can then be internalised by a copper transporter where it is transferred to copper chaperones for transport and specific delivery to various organelles. Of significance are internal copper transporters, ATP7A and ATP7B, notable for their role in disorders of copper deficiency and toxicity, Menkes and Wilson's disease, respectively. Metallothioneins and Cu/Zn superoxide dismutase can protect against excess copper in cells. It is clear too, increasing age, environmental and lifestyle factors impact on brain copper. Studies on AD suggest an important role for copper in the brain, with some AD therapies focusing on mobilising copper in AD brains. The transport of copper into the brain is complex and involves numerous players, including amyloid precursor protein, A beta peptide and cholesterol.
Macreadie
Ian G
IG
CSIRO Molecular and Health Technologies, 343 Royal Parade, Parkville, VIC, Australia. ian.macreadie@csiro.au
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001692:Biological Transport; D001921:Brain / Q000503:physiopathology; D027682:Cation Transport Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000378:metabolism / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000378:metabolism / Q000503:physiopathology; D008667:Metalloproteins / Q000378:metabolism*; D027701:Organic Cation Transport Proteins; D010088:Oxidoreductases / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D027682:Cation Transport Proteins; D008667:Metalloproteins; D027701:Organic Cation Transport Proteins; D003300:Copper; D002784:Cholesterol; D010088:Oxidoreductases; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases