alpha l-Antitrypsin deficiency and the hepatocytes - An elegans solution to drug discovery

作者：O'Reilly Linda P; Perlmutter David H; Silverman Gary A; Pak Stephen C^*

来源：International Journal of Biochemistry & Cell Biology, 2014, 47: 109-112.

DOI：10.1016/j.biocel.2013.12.006

• alpha 1-Antitrypsin deficiency
• Liver disease
• Hepatocyte
• C. elegans
• Protein aggregation

Hepatocytes are metabolically active cells of the liver that play an important role in the biosynthesis of proteins including alpha 1-antitrypsin. Mutations in the alpha 1-antitrypsin gene can lead to protein misfolding, polymerization/aggregation and retention of protein within the endoplasmic reticulum of hepatocytes. The intracellular accumulation of alpha 1-antitrypsin aggregates can lead to liver disease and increased likelihood of developing hepatocellular carcinomas. Of note, only similar to 10% of individuals with alpha 1-antitrypsin-deficiency develop severe liver disease suggesting that there are other genetic and/or environmental factors that determine disease outcome. The nematode, Caenorhabditis elegans, is a powerful genetic model organism to study molecular aspects of human disease. In this review, we discuss the functional similarities between the intestinal cells of C. elegans and human hepatocytes and how a C. elegans model of alpha 1-antitrypsin-deficiency can be used as a tool for identifying genetic modifiers and small molecule drugs.

• 出版日期2014-2