Abstract
A disintegrin and metalloproteinase 19 (ADAM19, or adamalysin 19) is a cell surface glycoprotein with a signal sequence, a prodomain, a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, a epidermal growth factor-like domain, a transmembrane domain, and a cytoplasmic domain. It is an endopeptidase that cleaves extracellular matrix proteins and sheds growth factors and cytokines such as neuregulins, heparin-binding epidermal growth factor, tumor necrosis factor (TNF)-α, and TNF-related activation-induced cytokine. The ADAM19 gene was cloned from human, monkey, and mouse. It is expressed in multiple organs and tissues including heart, lung, bones, brain, spleen, liver, skeletal muscle, kidney, and testes. ADAM19 plays essential roles in embryo implantation, cardiovascular morphogenesis, neurogenesis, and other developmental processes. It has constitutive α-secretase activity associated with processing Alzheimers disease amyloid precursor protein (APP) to non-amyloidogenic fragments; thus, it is neuroprotective. Those observations indicate that inhibition of ADAM19 activity is undesirable during embryo development and morphogenesis, and during the development of Alzheimers disease. On the contrary, in adults, ADAM19 is upregulated in human brain tumors such as astrocytoma and glioblastoma and is correlated with the invasiveness of glioma. It is also over-expressed by many human cancerous cell lines including cancers of the colon, ovary, lung, and brain. Abnormally high expression of ADAM19 is also linked to inflammation and fibrosis of the lung and kidney. Targeted inhibition of ADAM19 may be crucial for the treatment of certain types of tumors and inflammatory diseases.
Keywords: A disintegrin and metalloproteinase 19, meltrin β, ectodomain shedding, cardiovascular morphogenesis, neurogenesis, Alzheimer's disease, brain tumors, renal disease
Current Pharmaceutical Design
Title: ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Volume: 15 Issue: 20
Author(s): Bin Qi, Robert G. Newcomer and Qing-Xiang Amy Sang
Affiliation:
Keywords: A disintegrin and metalloproteinase 19, meltrin β, ectodomain shedding, cardiovascular morphogenesis, neurogenesis, Alzheimer's disease, brain tumors, renal disease
Abstract: A disintegrin and metalloproteinase 19 (ADAM19, or adamalysin 19) is a cell surface glycoprotein with a signal sequence, a prodomain, a metalloproteinase domain, a disintegrin domain, a cysteine-rich domain, a epidermal growth factor-like domain, a transmembrane domain, and a cytoplasmic domain. It is an endopeptidase that cleaves extracellular matrix proteins and sheds growth factors and cytokines such as neuregulins, heparin-binding epidermal growth factor, tumor necrosis factor (TNF)-α, and TNF-related activation-induced cytokine. The ADAM19 gene was cloned from human, monkey, and mouse. It is expressed in multiple organs and tissues including heart, lung, bones, brain, spleen, liver, skeletal muscle, kidney, and testes. ADAM19 plays essential roles in embryo implantation, cardiovascular morphogenesis, neurogenesis, and other developmental processes. It has constitutive α-secretase activity associated with processing Alzheimers disease amyloid precursor protein (APP) to non-amyloidogenic fragments; thus, it is neuroprotective. Those observations indicate that inhibition of ADAM19 activity is undesirable during embryo development and morphogenesis, and during the development of Alzheimers disease. On the contrary, in adults, ADAM19 is upregulated in human brain tumors such as astrocytoma and glioblastoma and is correlated with the invasiveness of glioma. It is also over-expressed by many human cancerous cell lines including cancers of the colon, ovary, lung, and brain. Abnormally high expression of ADAM19 is also linked to inflammation and fibrosis of the lung and kidney. Targeted inhibition of ADAM19 may be crucial for the treatment of certain types of tumors and inflammatory diseases.
Export Options
About this article
Cite this article as:
Qi Bin, Newcomer G. Robert and Sang Amy Qing-Xiang, ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases, Current Pharmaceutical Design 2009; 15 (20) . https://dx.doi.org/10.2174/138161209788682352
DOI https://dx.doi.org/10.2174/138161209788682352 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Thyroid Hormones Crosstalk with Growth Factors: Old Facts and New Hypotheses
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Subject Index To Volume 6
Central Nervous System Agents in Medicinal Chemistry Multifunctional Mesoporous Silica Nanoparticles for Combined Therapeutic, Diagnostic and Targeted Action in Cancer Treatment
Current Drug Targets Hedgehog Signaling and Urological Cancers
Current Drug Targets Regulating miRNA by Natural Agents as a New Strategy for Cancer Treatment
Current Drug Targets TGFß, a Potent Regulator of Tumor Microenvironment and Host Immune Response, Implication for Therapy
Current Molecular Medicine Ferroptosis: A Trusted Ally in Combating Drug Resistance in Cancer
Current Medicinal Chemistry Gene Selection in Multi-class Imbalanced Microarray Datasets Using Dynamic Length Particle Swarm Optimization
Current Bioinformatics Fibroblast Growth Factors/Fibroblast Growth Factor Receptors as Targets for the Development of Anti-Angiogenesis Strategies
Current Pharmaceutical Design Glioblastoma: Prognostic Factors and Predictive Response to Radio and Chemotherapy
Current Medicinal Chemistry Oxidative Stress in Schizophrenia
Current Neuropharmacology Matrine: Bioactivities and Structural Modifications
Current Topics in Medicinal Chemistry Meet Our Editorial Board Member
Current Medicinal Chemistry The use of Azoles Containing Natural Products in Cancer Prevention and Treatment: An Overview
Anti-Cancer Agents in Medicinal Chemistry mTOR: A Novel Therapeutic Target for Diseases of Multiple Systems
Current Drug Targets Flavonoid-Based Cancer Therapy: An Updated Review
Anti-Cancer Agents in Medicinal Chemistry Glioblastoma Stem-Like Cells – Isolation, Biology and Mechanisms of Chemotherapy Resistance
Current Signal Transduction Therapy Repurposed Drugs in Metabolic Disorders
Current Topics in Medicinal Chemistry Glucose-6-Phosphate Dehydrogenase Deficiency: Disadvantages and Possible Benefits
Cardiovascular & Hematological Disorders-Drug Targets Ribozymes, DNAzymes and Small Interfering RNAs as Therapeutics
Current Drug Targets