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Systems biology approach to Wilson’s disease

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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. 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.

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Acknowledgments

This work was supported by National Institute of Health grants R21 DK075659 and P01 GM067166 to SL. JLB is supported the sub-award to P20RR016466-10; LG is a recipient of the NRSA fellowship F31DK084730-02.

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  1. University of Alaska Anchorage, Anchorage, AK, 99508, USA

    Jason L. Burkhead

  2. Department of Physiology, Johns Hopkins University, Baltimore, MD, 21230, USA

    Lawrence W. Gray & Svetlana Lutsenko

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  1. Jason L. Burkhead
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  2. Lawrence W. Gray
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Correspondence to Svetlana Lutsenko.

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Burkhead, J.L., Gray, L.W. & Lutsenko, S. Systems biology approach to Wilson’s disease. Biometals 24, 455–466 (2011). https://doi.org/10.1007/s10534-011-9430-9

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