caa a22 4500 445321547 CHVBK 20180317142705.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10534-011-9430-9 doi (NATIONALLICENCE)springer-10.1007/s10534-011-9430-9 Systems biology approach to Wilson's disease [Elektronische Daten] [Jason Burkhead, Lawrence Gray, Svetlana Lutsenko] Wilson's disease (WD) is a severe disorder of copper misbalance, which manifests with a wide spectrum of liver pathology and/or neurologic and psychiatric symptoms. WD is caused by mutations in a gene encoding a copper-transporting ATPase ATP7B and is accompanied by accumulation of copper in tissues, especially in the liver. Copper-chelation therapy is available for treatment of WD symptoms and is often successful, however, significant challenges remain with respect to timely diagnostics and treatment of the disease. The lack of genotype-phenotype correlation remains unexplained, the causes of fulminant liver failure are not known, and the treatment of neurologic symptoms is only partially successful, underscoring the need for better understanding of WD mechanisms and factors that influence disease manifestations. Recent gene and protein profiling studies in animal models of WD began to uncover cellular processes that are primarily affected by copper accumulation in the liver. The results of such studies, summarized in this review, revealed new molecular players and pathways (cell cycle and cholesterol metabolism, mRNA splicing and nuclear receptor signaling) linked to copper misbalance. A systems biology approach promises to generate a comprehensive view of WD onset and progression, thus helping with a more fine-tune treatment and monitoring of the disorder. Springer Science+Business Media, LLC., 2011 Wilson's disease nationallicence Array nationallicence Copper nationallicence LEC rat nationallicence ATP7B nationallicence Proteomics nationallicence Burkhead Jason University of Alaska Anchorage, 99508, Anchorage, AK, USA aut Gray Lawrence Department of Physiology, Johns Hopkins University, 21230, Baltimore, MD, USA aut Lutsenko Svetlana Department of Physiology, Johns Hopkins University, 21230, Baltimore, MD, USA aut BioMetals Springer Netherlands 24/3(2011-06-01), 455-466 0966-0844 24:3<455 2011 24 10534 https://doi.org/10.1007/s10534-011-9430-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10534-011-9430-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Burkhead Jason University of Alaska Anchorage, 99508, Anchorage, AK, USA aut NATIONALLICENCE 700 1- Gray Lawrence Department of Physiology, Johns Hopkins University, 21230, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Lutsenko Svetlana Department of Physiology, Johns Hopkins University, 21230, Baltimore, MD, USA aut NATIONALLICENCE 773 0- BioMetals Springer Netherlands 24/3(2011-06-01), 455-466 0966-0844 24:3<455 2011 24 10534 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer