imprint:
[Erscheinungsort nicht ermittelbar]: Utrecht University, 2007
Language:
English
Origination:
University thesis:
Dissertation, Utrecht University, 2007
Footnote:
Description:
Copper is an essential element for living organisms, yet it is very toxic when present in amounts exceeding cellular needs. Delicate mechanisms have evolved to ensure proper copper homeostasis is maintained for the organism, as well as at a cellular level, and perturbations in these mechanisms give rise to several severe diseases of copper homeostasis. However, the exact mechanisms through which such disorders of copper homeostasis develop are not completely understood. Therefore, the work in this thesis entitled Novel insights in the molecular pathogenesis of human copper homeostasis disorders through studies of protein-protein interactions" aims to dissect the molecular pathogenesis of human copper homeostasis disorders. Copper deficiency, as caused by mutations in ATP7A in Menkes disease, manifests with neurological degeneration, growth defects and several other symptoms that directly relate to dysfunction of copper-dependent enzymes. Copper overload is observed in several different disorders in man. Wilson disease, for example, is caused by mutations in ATP7B and manifests with copper accumulation in the liver and brain, resulting in extensive hepatic and neurological defects. Other copper overload disorders comprise Indian childhood cirrhosis (ICC), endemic infantile Tyrolean cirrhosis (ETIC) and idiopathic copper toxicosis (ICT), caused by both excessive copper intake and an uncharacterized genetic predisposition. Recently, we identified COMMD1 as a novel protein involved in copper homeostasis