The copper ATPases : intracellular trafficking and nervous system function

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Copper is essential for life, as it participates as a cofactor in numerous enzymatic reactions including energy generation, antioxidant defense, neurotransmitter synthesis and iron metabolism. Mutations in proteins that regulate intracellular copper concentrations cause several human diseases. For example, mutations in the copper transporting ATPase, ATP7A, underlie 2 diseases; Menkes disease, and X-linked spinal muscular atrophy type 3 (SMAX-3). Menkes patients suffer from severe systemic copper deficiency caused by an inability to transport copper out of the intestine to the rest of the body, and exhibit severe neurodegeneration. SMAX-3 is a progressive hereditary motor neuropathy, caused by partial loss-of function mutations in ATP7A. While research into the tissue-specific roles of the copper transporters within the central and peripheral nervous systems will help elucidate improved therapeutics for these diseases, it is also clear that findings will have a much broader significance due to the various roles of copper in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and Huntington's disease.