Abstract
Alpha-1 antitrypsin (A1AT) is a 52-kDa, acute phase glycoprotein encoded by the protease inhibitor (PI) locus, located on the long arm of chromosome 14 (14q31-32.3). Its structure is composed of a total of 7 exons, 4 coding (II, III, IV, and V) and 3 non-coding (IA, IB, and IC).
A1AT is produced primarily by hepatocytes and acts as a serine protease inhibitor with antiprotease and immunoregulatory activities. The main target of A1AT is neutrophil elastase (NE), an enzyme released during a neutrophil-mediated inflammatory process. When the enzyme is not adequately balanced by A1AT activity, it can cause tissue injury and destruction.
A1AT deficiency (A1ATD) is a genetic autosomal recessive disease, characterized by low serum levels of A1AT. The condition may lead to liver disease, early-onset pulmonary emphysema and, rare multi-organ vasculitis, necrotizing panniculitis and fibromyalgia.
At least 100 allelic variants of the polymorphic PI locus have been described with groups including associations with different A1AT plasma levels and functions.
Treatments with purified A1AT preparations, obtained through pooled human plasma (augmentation therapy), have been proven to improve survival and disease-related quality of life, as well as, slow down the progression of organ damage. Furthermore, ongoing research is now focusing on the development of specifically targeted, new medications.
The aim of this review is to summarize our knowledge of the genetic A1AT variants, focusing on their variable clinical manifestation, report routine and recently updated laboratory diagnostic techniques, and to highlight the relevance of early diagnosis of A1ATD. Moreover, we will review the role of augmentation therapy recommendations and future perspectives focusing on a personalized treatment of A1ATD.
Keywords: Alpha-1 antitrypsin, neutrophil elastase, genetic variants, liver disease, chronic obstructive pulmonary disease, serine protease inhibitor superfamily (SERPIN), polymers.
Current Medicinal Chemistry
Title:Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches
Volume: 24 Issue: 1
Author(s): Simona Santangelo, Simone Scarlata, Maria L. Poeta, Adam J. Bialas, Gregorino Paone and Raffaele Antonelli Incalzi
Affiliation:
Keywords: Alpha-1 antitrypsin, neutrophil elastase, genetic variants, liver disease, chronic obstructive pulmonary disease, serine protease inhibitor superfamily (SERPIN), polymers.
Abstract: Alpha-1 antitrypsin (A1AT) is a 52-kDa, acute phase glycoprotein encoded by the protease inhibitor (PI) locus, located on the long arm of chromosome 14 (14q31-32.3). Its structure is composed of a total of 7 exons, 4 coding (II, III, IV, and V) and 3 non-coding (IA, IB, and IC).
A1AT is produced primarily by hepatocytes and acts as a serine protease inhibitor with antiprotease and immunoregulatory activities. The main target of A1AT is neutrophil elastase (NE), an enzyme released during a neutrophil-mediated inflammatory process. When the enzyme is not adequately balanced by A1AT activity, it can cause tissue injury and destruction.
A1AT deficiency (A1ATD) is a genetic autosomal recessive disease, characterized by low serum levels of A1AT. The condition may lead to liver disease, early-onset pulmonary emphysema and, rare multi-organ vasculitis, necrotizing panniculitis and fibromyalgia.
At least 100 allelic variants of the polymorphic PI locus have been described with groups including associations with different A1AT plasma levels and functions.
Treatments with purified A1AT preparations, obtained through pooled human plasma (augmentation therapy), have been proven to improve survival and disease-related quality of life, as well as, slow down the progression of organ damage. Furthermore, ongoing research is now focusing on the development of specifically targeted, new medications.
The aim of this review is to summarize our knowledge of the genetic A1AT variants, focusing on their variable clinical manifestation, report routine and recently updated laboratory diagnostic techniques, and to highlight the relevance of early diagnosis of A1ATD. Moreover, we will review the role of augmentation therapy recommendations and future perspectives focusing on a personalized treatment of A1ATD.
Export Options
About this article
Cite this article as:
Santangelo Simona, Scarlata Simone, Poeta L. Maria, Bialas J. Adam, Paone Gregorino and Incalzi Antonelli Raffaele, Alpha-1 Antitrypsin Deficiency: Current Perspective from Genetics to Diagnosis and Therapeutic Approaches, Current Medicinal Chemistry 2017; 24 (1) . https://dx.doi.org/10.2174/0929867324666161118125827
DOI https://dx.doi.org/10.2174/0929867324666161118125827 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Lipid-Induced Modulation of Protective Signalling Pathways in Cardiovascular Disease: The Role of High Density Lipoproteins
Current Signal Transduction Therapy An Overview of Published Papers and Important Developments in the Past Three Years
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry The Genetics of Small-Vessel Disease
Current Medicinal Chemistry Kawasaki Disease and Its Treatment – An Update
Current Rheumatology Reviews Rheumatoid Arthritis: Notable Biomarkers Linking to Chronic Systemic Conditions and Cancer
Current Pharmaceutical Design Ginger and Heart Health: From Mechanisms to Therapeutics
Current Molecular Pharmacology Prognostic Parameters for Symptomatic Intracranial Hemorrhage after Intravenous Thrombolysis in Acute Ischemic Stroke in an Asian Population
Current Neurovascular Research Randomized Controlled Trials in Steroid Dependent and in Severe Colitis
Reviews on Recent Clinical Trials Effect of Aging on Metabolic Pathways in Endothelial Progenitor Cells
Current Pharmaceutical Design The Neuroprotective Role of PEDF: Implication for the Therapy of Neurological Disorders
Current Molecular Medicine Nutraceuticals and their Novel Drug Delivery System: A Boon to Human Health
Current Nutrition & Food Science Anti-Inflammatory and Anti-Neoplastic Actions of Resveratrol
Current Nutrition & Food Science Fibrates and Microvascular Complications in Diabetes - Insight from the FIELD Study
Current Pharmaceutical Design Heat Shock Proteins: Therapeutic Perspectives in Inflammatory Disorders
Recent Patents on Inflammation & Allergy Drug Discovery A Simple and Rapid Method for Expression and Purification of Functional TNF-α Using GST Fusion System
Current Pharmaceutical Biotechnology Astrocyte`s RAGE: More Than Just a Question of Mood
Central Nervous System Agents in Medicinal Chemistry Augmentation Therapy with Alpha1-antitrypsin: Novel Perspectives
Cardiovascular & Hematological Disorders-Drug Targets Clinical Queries Addressed in Patients with Systemic Autoimmune Diseases. Can Cardiovascular Magnetic Resonance Give the Final Solution?
Inflammation & Allergy - Drug Targets (Discontinued) Multimodalities Imaging of Immunoglobulin 4-related Cardiovascular Disorders
Current Cardiology Reviews Viral Anti-Inflammatory Reagents: The Potential for Treatment of Arthritic and Vasculitic Disorders
Endocrine, Metabolic & Immune Disorders - Drug Targets