scholarly journals The Role of Autophagy in Alpha-1-Antitrypsin Deficiency: A Specific Cellular Response in Genetic Diseases Associated with Aggregation-Prone Proteins

Autophagy ◽  
2006 ◽  
Vol 2 (4) ◽  
pp. 258-263 ◽  
Author(s):  
David H. Perlmutter
Keyword(s):  
Cellular Response ◽  
Genetic Diseases ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals DGKα in Neutrophil Biology and Its Implications for Respiratory Diseases

2019 ◽  
Vol 20 (22) ◽  
pp. 5673 ◽  
Author(s):  
Gianluca Baldanzi ◽  
Mario Malerba
Keyword(s):  
Respiratory Diseases ◽  
Genetic Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Rare Genetic Diseases ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Diacylglycerol kinases (DGKs) play a key role in phosphoinositide signaling by removing diacylglycerol and generating phosphatidic acid. Besides the well-documented role of DGKα and DGKζ as negative regulators of lymphocyte responses, a robust body of literature points to those enzymes, and specifically DGKα, as crucial regulators of leukocyte function. Upon neutrophil stimulation, DGKα activation is necessary for migration and a productive response. The role of DGKα in neutrophils is evidenced by its aberrant behavior in juvenile periodontitis patients, which express an inactive DGKα transcript. Together with in vitro experiments, this suggests that DGKs may represent potential therapeutic targets for disorders where inflammation, and neutrophils in particular, plays a major role. In this paper we focus on obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD), but also rare genetic diseases such as alpha-1-antitrypsin deficiency. Indeed, the biological role of DGKα is understudied outside the T lymphocyte field. The recent wave of research aiming to develop novel and specific inhibitors as well as KO mice will allow a better understanding of DGK’s role in neutrophilic inflammation. Better knowledge and pharmacologic tools may also allow DGK to move from the laboratory bench to clinical trials.

scholarly journals In Vitro Investigations on Optimizing and Nebulization of IVT-mRNA Formulations for Potential Pulmonary-Based Alpha-1-Antitrypsin Deficiency Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1281
Author(s):  
Shan Guan ◽  
Max Darmstädter ◽  
Chuanfei Xu ◽  
Joseph Rosenecker
Keyword(s):  
Epithelial Cells ◽  
Transfection Efficiency ◽  
Genetic Diseases ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Significant Toxicity ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

In vitro-transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The nebulized formulations of IVT-mRNA-encoding alpha-1-antitrypsin (A1AT-mRNA) would be a highly acceptable and tolerable remedy for the protein replacement therapy for alpha-1-antitrypsin deficiency in the future. Here we show that lipoplexes containing A1AT-mRNA prepared in optimum conditions could successfully transfect human bronchial epithelial cells without significant toxicity. A reduction in transfection efficiency was observed for aerosolized lipoplexes that can be partially overcome by increasing the initial number of components. A1AT produced from cells transfected by nebulized A1AT-mRNA lipoplexes is functional and could successfully inhibit the enzyme activity of trypsin as well as elastase. Our data indicate that aerosolization of A1AT-mRNA therapy constitutes a potentially powerful means to transfect airway epithelial cells with the purpose of producing functional A1AT, while bringing along the unique advantages of IVT-mRNA.

scholarly journals Alpha-1 Antitrypsin Deficiency: Principles of Care

2020 ◽  
Vol 33 (6) ◽  
pp. 433
Author(s):  
Joana F. Rodrigues ◽  
Alexandra Mineiro ◽  
António Reis ◽  
David G. Ventura ◽  
Fernando Fernandez-Llimos ◽  
...  
Keyword(s):  
Proteinase Inhibitor ◽  
Clinical Care ◽  
High Standard ◽  
Access To Treatment ◽  
Presenting Symptoms ◽  
Patient Organizations ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

Alpha-1 antitrypsin deficiency is an autosomal co-dominant inherited disorder that results in decreased circulating levels of alpha-1 antitrypsin (also known as alpha-1 proteinase inhibitor) and predisposes affected individuals to early onset lung and liver disease. There is currently no cure for alpha-1 antitrypsin deficiency. However, appropriate treatment and a high standard of clinical care can prevent patients from being seriously affected and having to undergo major medical interventions, such as organ transplantation. Beyond managing the symptoms associated with alpha-1 antitrypsin deficiency, alpha-1 proteinase inhibitor therapy is the only treatment for the condition’s underlying cause. Early diagnosis is important to ensure efficient therapeutic strategies and to minimize further deterioration of lung function. alpha-1 antitrypsin deficiency is under diagnosed globally, partly because the disease has no unique presenting symptoms. This document was prepared by a Portuguese multidisciplinary group and it aims to set out comprehensive principles of care for Alpha-1 antitrypsin deficiency. These include the importance of registries, the need for clinical research, the need for consistent recommendations (regarding diagnosis, treatment and monitoring), the role of reference centres, the requirement for sustained access to treatment, diagnostic and support services, and the role of patient organizations.

scholarly journals The Role of Computed Tomography for the Evaluation of Lung Disease in Alpha-1 Antitrypsin Deficiency

CHEST Journal ◽  
2018 ◽  
Vol 153 (5) ◽  
pp. 1240-1248 ◽  
Author(s):  
Michael A. Campos ◽  
Alejandro A. Diaz
Keyword(s):  
Computed Tomography ◽  
Lung Disease ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals The role of bronchial epithelial cells in the pathogenesis of COPD in Z-alpha-1 antitrypsin deficiency

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Laura Pini ◽  
Laura Tiberio ◽  
Narayanan Venkatesan ◽  
Michela Bezzi ◽  
Luciano Corda ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

The Role of Neutrophils in Alpha-1 Antitrypsin Deficiency

2016 ◽  
Vol 13 (Supplement_4) ◽  
pp. S297-S304 ◽  
Author(s):  
Cormac McCarthy ◽  
Emer P. Reeves ◽  
Noel G. McElvaney
Keyword(s):  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

scholarly journals Hepatocyte proteomes reveal the role of protein disulfide isomerase 4 in alpha 1-antitrypsin deficiency

JHEP Reports ◽  
2021 ◽  
pp. 100297
Author(s):  
Esra Karatas ◽  
Anne-Aurélie Raymond ◽  
Céline Leon ◽  
Jean-William Dupuy ◽  
Sylvaine Di-Tommaso ◽  
...  
Keyword(s):  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Protein Disulfide

The Role of Autophagy in Alpha-1-Antitrypsin Deficiency

2011 ◽  
pp. 33-54 ◽  
Author(s):  
Tunda Hidvegi ◽  
Amitava Mukherjee ◽  
Michael Ewing ◽  
Carolyn Kemp ◽  
David H. Perlmutter
Keyword(s):  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin
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