An Autophagy-Enhancing Drug Promotes Degradation of Mutant α 1 -Antitrypsin Z and Reduces Hepatic Fibrosis
| Autor: | Michael Ewing, Caroline Beckett, Christine S. Dippold, Christina Goldbach, Simon C. Watkins, Carolyn Kemp, Nicholas Maurice, Tunda Hidvegi, Amitava Mukherjee, George K. Michalopoulos, Pamela Hale, David H. Perlmutter |
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| Rok vydání: | 2010 |
| Předmět: |
Liver Cirrhosis
Proteasome Endopeptidase Complex Protein Folding medicine.medical_specialty Transgene Mutant Mice Transgenic Biology Endoplasmic Reticulum medicine.disease_cause Cell Line Mice Phagosomes alpha 1-Antitrypsin Deficiency Internal medicine Autophagy medicine Animals Humans Mutation Multidisciplinary Point mutation Disease Models Animal Carbamazepine Phenotype Endocrinology Liver Solubility Mechanism of action alpha 1-Antitrypsin Cancer research Mutant Proteins medicine.symptom Hepatic fibrosis Carcinogenesis HeLa Cells |
| Zdroj: | Science. 329:229-232 |
| ISSN: | 1095-9203 0036-8075 |
| DOI: | 10.1126/science.1190354 |
| Popis: | Correcting a Liver Problem The classical form of α 1 -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. (p. 229 , published online June 3; 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. |
| Databáze: | OpenAIRE |
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