Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: a meeting review.
In recent years, we have witnessed several important paradigm shifts in understanding the molecular basis of liver disease in alpha-1-antitrypsin (AT) deficiency. These shifts have become possible as a result of a number of advances in research on the cell biology of aggregation-prone mutant proteins and in research on the pathobiological mechanisms of liver disease in general. Late-breaking research in these areas was the subject of an AASLD/Alpha-1 Foundation Single Topic Conference in Atlanta, Georgia, on January 26 to 28, 2006. The conference was titled "Alpha-1-Antitrypsin Deficiency and Other Liver Diseases Caused by Aggregated Proteins." Investigators from all over the world, representing a broad array of scientific disciplines and perspectives, discussed the pathobiology of AT deficiency, mechanisms of cell injury in diseases associated with aggregation-prone proteins, pathways by which cells respond to protein aggregation and mislocalization, and mechanisms of liver injury in general and in diseases related to AT deficiency. A session of the meeting was devoted to novel therapeutic strategies being developed for AT deficiency as well as to strategies either in development or already being applied to the class of diseases associated with mutant proteins.
Perlmutter
David H
DH
Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA. david.perlmutter@chp.edu
Brodsky
Jeffrey L
JL
Balistreri
William F
WF
Trapnell
Bruce C
BC
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006505:Hepatitis / Q000503:physiopathology; D006801:Humans; D008107:Liver Diseases / Q000503:physiopathology*; D008113:Liver Neoplasms / Q000209:etiology; D017354:Point Mutation; D011489:Protein Denaturation; D017510:Protein Folding; D015398:Signal Transduction; D000515:alpha 1-Antitrypsin / Q000235:genetics; D019896:alpha 1-Antitrypsin Deficiency / Q000503:physiopathology* / Q000628:therapy
D000515:alpha 1-Antitrypsin