Systems biology approach to Wilson's disease

Jason L. Burkhead, Lawrence W. Gray, Svetlana Lutsenko

Research output: Contribution to journalArticle

Abstract

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. Copperchelation 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.

Original languageEnglish (US)
Pages (from-to)455-466
Number of pages12
JournalBioMetals
Volume24
Issue number3
DOIs
StatePublished - Jun 2011

Fingerprint

hepatolenticular degeneration
Hepatolenticular Degeneration
Systems Biology
Biological Sciences
copper
Copper
Liver
signs and symptoms (animals and humans)
Neurologic Manifestations
nervous system
liver
liver failure
cholesterol metabolism
Acute Liver Failure
Genetic Association Studies
Cytoplasmic and Nuclear Receptors
Gene encoding
adenosinetriphosphatase
Psychiatry
Disease Progression

Keywords

  • Array
  • ATP7B
  • Copper
  • LEC rat
  • Proteomics
  • Wilson's disease

ASJC Scopus subject areas

  • Biomaterials
  • Metals and Alloys
  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Systems biology approach to Wilson's disease. / Burkhead, Jason L.; Gray, Lawrence W.; Lutsenko, Svetlana.

In: BioMetals, Vol. 24, No. 3, 06.2011, p. 455-466.

Research output: Contribution to journalArticle

Burkhead, Jason L. ; Gray, Lawrence W. ; Lutsenko, Svetlana. / Systems biology approach to Wilson's disease. In: BioMetals. 2011 ; Vol. 24, No. 3. pp. 455-466.
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