Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease
Alpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is a protein mainly produced and secreted by hepatocytes. Some specific mutations affecting SERPINA1 may cause accumulation of misfolded AAT in the endoplasmic reticulum of the hepatocytes leading to AAT deficiency (AATD). Z-AAT is the most s...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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European Medical Journal
2019-05-01
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| Series: | European Medical Journal Hepatology |
| Subjects: | |
| Online Access: | https://www.emjreviews.com/hepatology/article/overview-of-alpha-1-antitrypsin-deficiency-mediated-liver-disease/ |
| _version_ | 1818043600693362688 |
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| author | Esra Karatas Sylvaine Di-Tommaso Nathalie Dugot-Senant Alain Lachaux Marion Bouchecareilh |
| author_facet | Esra Karatas Sylvaine Di-Tommaso Nathalie Dugot-Senant Alain Lachaux Marion Bouchecareilh |
| author_sort | Esra Karatas |
| collection | DOAJ |
| description | Alpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is a protein mainly produced and secreted by hepatocytes. Some specific mutations affecting SERPINA1 may cause accumulation of misfolded AAT in the endoplasmic reticulum of the hepatocytes leading to AAT deficiency (AATD). Z-AAT is the most severe and common deficient variant. This mutant is not only retained in the endoplasmic reticulum but accumulates as an aggregate that triggers a cascade of intracellular signalling pathways inducing hepatocyte injury and death. Nevertheless, among all the homozygous ZZ patients only 15% develop liver injury, with a wide-range of disease severities ranging from hepatic fibrosis to cirrhosis or even hepatocellular carcinoma. Due to the lack of knowledge surrounding modifiers associated with Z-AAT-mediated hepatocyte toxicity, it is impossible to screen for AATD patients at risk of liver damage and to develop accurate therapeutic strategies. This review aims to give an overview and update our knowledge of AATD associated with liver disease and discusses possible new therapeutic strategies. |
| first_indexed | 2024-12-10T09:04:48Z |
| format | Article |
| id | doaj.art-f9abb2512c9d44fea87c05bfa8e8fa4d |
| institution | Directory Open Access Journal |
| issn | 2053-4221 |
| language | English |
| last_indexed | 2024-12-10T09:04:48Z |
| publishDate | 2019-05-01 |
| publisher | European Medical Journal |
| record_format | Article |
| series | European Medical Journal Hepatology |
| spelling | doaj.art-f9abb2512c9d44fea87c05bfa8e8fa4d2022-12-22T01:55:11ZengEuropean Medical JournalEuropean Medical Journal Hepatology2053-42212019-05-01716579Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver DiseaseEsra Karatas0Sylvaine Di-Tommaso1Nathalie Dugot-Senant2Alain Lachaux3Marion Bouchecareilh4INSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Université de Bordeaux, Bordeaux, FranceOncoprot, INSERM 1053, TBM-Core US 005, Université de Bordeaux, Bordeaux, FrancePlateforme d'histopathologie, TBM-Core US 005, Université de Bordeaux, Bordeaux, FranceHépatologie, Gastroentérologie et Nutrition pédiatriques, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon, France; Faculté de Médecine Lyon-Est, Université Claude Bernard Lyon 1, Lyon, FranceINSERM, UMR1053 Bordeaux Research in Translational Oncology (BaRITOn), Université de Bordeaux, Bordeaux, FranceAlpha-1 antitrypsin (AAT), encoded by the SERPINA1 gene, is a protein mainly produced and secreted by hepatocytes. Some specific mutations affecting SERPINA1 may cause accumulation of misfolded AAT in the endoplasmic reticulum of the hepatocytes leading to AAT deficiency (AATD). Z-AAT is the most severe and common deficient variant. This mutant is not only retained in the endoplasmic reticulum but accumulates as an aggregate that triggers a cascade of intracellular signalling pathways inducing hepatocyte injury and death. Nevertheless, among all the homozygous ZZ patients only 15% develop liver injury, with a wide-range of disease severities ranging from hepatic fibrosis to cirrhosis or even hepatocellular carcinoma. Due to the lack of knowledge surrounding modifiers associated with Z-AAT-mediated hepatocyte toxicity, it is impossible to screen for AATD patients at risk of liver damage and to develop accurate therapeutic strategies. This review aims to give an overview and update our knowledge of AATD associated with liver disease and discusses possible new therapeutic strategies.https://www.emjreviews.com/hepatology/article/overview-of-alpha-1-antitrypsin-deficiency-mediated-liver-disease/alpha-1 antitrypsin deficiencygenetic and environmental modifiersliver diseasepaediatricrare inherited disordertherapeutic strategies |
| spellingShingle | Esra Karatas Sylvaine Di-Tommaso Nathalie Dugot-Senant Alain Lachaux Marion Bouchecareilh Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease European Medical Journal Hepatology alpha-1 antitrypsin deficiency genetic and environmental modifiers liver disease paediatric rare inherited disorder therapeutic strategies |
| title | Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease |
| title_full | Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease |
| title_fullStr | Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease |
| title_full_unstemmed | Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease |
| title_short | Overview of Alpha-1 Antitrypsin DeficiencyMediated Liver Disease |
| title_sort | overview of alpha 1 antitrypsin deficiencymediated liver disease |
| topic | alpha-1 antitrypsin deficiency genetic and environmental modifiers liver disease paediatric rare inherited disorder therapeutic strategies |
| url | https://www.emjreviews.com/hepatology/article/overview-of-alpha-1-antitrypsin-deficiency-mediated-liver-disease/ |
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