Alpha-1 Antitrypsin Deficiency —From Genes to Therapies

NIH funded research has identified genetic factors and clinical manifestations of alpha-1 antitrypsin deficiency which may lead to future treatments.
Source: NIDDK News - Category: Endocrinology Source Type: news

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Conclusion: Our results suggest that AAT is internalized by β cells through clathrin-mediated endocytosis that leads to the suppression of caspase 9 activation. This process is required for the protective function of AAT in islets when challenged with proinflammatory cytokines or after islet transplantation.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Conclusions: Our data revealed the significance of targeting PRMT5 activity in LCSC elimination and HCC differentiation, and proposed that DW14800 may represent a promising therapeutic agent for HCC in the clinic.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Conclusion: Our data reveal molecular epigenetic signatures within this mutationally homogeneous group that point to ways to stratify patients for liver disease risk.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by array Homo sapiens Source Type: research
AbstractAlpha-1 antitrypsin (AAT) protects the lung by inhibiting neutrophil proteinases, but AAT has many other non-proteolytic functions that are anti-inflammatory, antiviral and homeostatic. Approximately 1 in 1600 to 1 in 5000 people have the homozygous Z mutation, which causes AAT misfolding, accumulation in (predominantly) liver cells and low circulating levels of AAT, leading to AAT deficiency (AATD). AATD is classically a disease of neutrophilic inflammation, with an aggressive and damaging innate immune response contributing to emphysema and other pathologies. AATD is one of the most common genetic disorders but c...
Source: Drugs and Aging - Category: Geriatrics Source Type: research
Abstract Previous proteomic studies have identified alpha 1-antitrypsin (A1AT) as a potential serum biomarker for colorectal cancer (CRC). In this case-control study, we evaluated plasma A1AT concentration and activity as a biomarker for the early diagnosis of colorectal cancer in a group of 113 sporadic CRC patients. We also analyzed A1AT gene promoter methylation, and genotypes in this group of CRC patients. The plasma A1AT and CEA concentrations were measured using the nephelometric and ELISA methods, respectively. A1AT activity was determined by Trypsin Inhibitor Capacity assay. The genomic DNA from blood samp...
Source: Pathology Oncology Research - Category: Pathology Authors: Tags: Pathol Oncol Res Source Type: research
We examined the relation between increased hepcidin secretion, the known hepcidin regulators and the signalling pathways controlled by fractalkine receptor. Our data revealed that TMPRSS6 and alpha 1-antitrypsin levels decreased due to fractalkine treatment, as well as the activity of NFκB pathway and the tyrosine phosphorylation of STAT5 factor. Moreover, fractalkine-induced hepcidin production of microglia initiated ferroportin internalisation of SH-SY5Y cells, which contributed to iron accumulation of neurons. Our results demonstrate that soluble form of fractalkine regulates hepcidin expression of BV-2 cells thro...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
ConclusionsWe hypothesize that chronic, multifocal inflammation in the skin in the setting of immunosuppression led to simultaneous, malignant transformation in numerous skin lesions. We discuss the challenges of diagnosing pleomorphic dermal sarcoma, therapeutic options, and stress the need for multidisciplinary management of these cases.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
Alpha-1 antitrypsin deficiency (AATD) accounts for 5% of lung transplants performed worldwide. Ireland has a high frequency of 1 in 25 for the Z allele and 1 in 10 for the S allele [1]. These variants are associated with decreased production of alpha-1 antitrypsin (AAT), which predisposes to unprotected proteolytic activity of neutrophil elastase (NE) and proteinase 3 (PR3), linked to an increased risk of emphysema and hepatic disease. Associated inflammatory conditions such as vasculitis, panniculitis and inflammatory bowel disease are also suspected to be caused by uncontrolled neutrophil proteinase activity [2–4]....
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Original Articles: Research letters Source Type: research
PMID: 31063431 [PubMed - as supplied by publisher]
Source: American Journal of Respiratory and Critical Care Medicine - Category: Respiratory Medicine Authors: Tags: Am J Respir Crit Care Med Source Type: research
Conclusions: While there is a certain overlap between the results of the current study and published transcriptomic profiles of non-transplanted livers with steatosis, we have identified discrete characteristics of the non-alcoholic fatty liver disease in liver grafts potentially utilizable for the establishment of predictive signature. Introduction Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in industrialized countries, its prevalence being estimated at 19–31.3% (1). It encompasses a range of conditions that are thought to arise from fatty liver (simple steatosis) throu...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
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