Alpha-1-Antitrypsin Deficiency: Importance of Proteasomal and Autophagic Degradative Pathways in Disposal of Liver Disease–Associated Protein Aggregates

Annual Review of Medicine - Tập 62 Số 1 - Trang 333-345 - 2011
David H. Perlmutter1
1Departments of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15217;

Tóm tắt

Alpha-1-antitrypsin (AT) deficiency is the most common genetic cause of liver disease in children. The primary pathological issue is a point mutation that renders an abundant hepatic secretory glycoprotein prone to altered folding and a tendency to polymerize and aggregate. However, the expression of serious liver damage among homozygotes is dependent on genetic and/or environmental modifiers. Several studies have validated the concept that endogenous hepatic pathways for disposal of aggregation-prone proteins, including the proteasomal and autophagic degradative pathways, could play a key role in the variation in hepatic damage and be the target of the modifiers. Exciting recent results have shown that a drug that enhances autophagy can reduce the hepatic load of aggregated protein and reverse fibrosis in a mouse model of this disease.

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Annual Review of Medicine

Tập 62 Số 1

333-345

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