Editors' ChoiceMEDICINE

Correcting a Liver Problem

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Science Signaling  13 Jul 2010:
Vol. 3, Issue 130, pp. ec211
DOI: 10.1126/scisignal.3130ec211

The classical form of α1-antitrypsin (AT) deficiency is caused by a point mutation that alters the folding and causes intracellular aggregation of AT—an abundant liver-derived plasma glycoprotein. AT deficiency is the most common genetic cause of liver disease in childhood and can also lead to cirrhosis and/or hepatocellular carcinoma in adulthood. Carbamazepine is a drug known to be well tolerated in humans that enhances the intracellular degradation process known as autophagy. Now, Hidvegi et al. (see the Perspective by Sifers) show that carbamazepine can reduce the severity of liver disease in a mouse model of AT deficiency by enhancing the degradation of misfolded accumulated AT.

T. Hidvegi, M. Ewing, P. Hale, C. Dippold, C. Beckett, C. Kemp, N. Maurice, A. Mukherjee, C. Goldbach, S. Watkins, G. Michalopoulos, D. H. Perlmutter, An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis. Science 329, 229–232 (2010). [Abstract] [Full Text]

R. N. Sifers, Clearing conformational disease. Science 329, 154–155 (2010). [Summary] [Full Text]

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