Abstract
Transforming growth factor-β family members, which include TGF-βs, activins and bone morphogenetic proteins (BMPs), play important roles in development and maintaining tissue homeostasis. The extracellular TGF-β family members signal across the plasmamembrane by activating type I and type II serine/threonine kinase receptors. Pertubation in TGF-β family receptor signaling has been implicated in certain diseases, including musculo-skeletal disorders. Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by progressive formation of ectopic bone and congenital malformations of the great toes. At present no curative therapy is available, therefore prevention of heterotopic ossification is the hallmark of FOP management. FOP has been linked to an autosomal dominant mutation on chromosome 2, to the gene encoding activin receptor-like kinase 2 (ALK2), a BMP type I receptor. This mutation is found in almost all classically affected FOP patients and causes the FOP phenotype. This discovery has paved the way for further investigations into the molecular basis underlying FOP and has recently pointed towards potential strategies to treat this devastating disease.
Keywords: BMP, Fibrodysplasia ossificans progressiva, heterotopic ossification, activin receptor-like kinase 2, ALK2 R206H, osteoblast differentiation, Transforming growth factor-β, tissue homeostasis, mutation, chromosome 2.
Current Pharmaceutical Design
Title:Deregulated Bone Morphogenetic Protein Receptor Signaling Underlies Fibrodysplasia Ossificans Progressiva
Volume: 18 Issue: 27
Author(s): David J.J. de Gorter, Vishant Jankipersadsing and Peter ten Dijke
Affiliation:
Keywords: BMP, Fibrodysplasia ossificans progressiva, heterotopic ossification, activin receptor-like kinase 2, ALK2 R206H, osteoblast differentiation, Transforming growth factor-β, tissue homeostasis, mutation, chromosome 2.
Abstract: Transforming growth factor-β family members, which include TGF-βs, activins and bone morphogenetic proteins (BMPs), play important roles in development and maintaining tissue homeostasis. The extracellular TGF-β family members signal across the plasmamembrane by activating type I and type II serine/threonine kinase receptors. Pertubation in TGF-β family receptor signaling has been implicated in certain diseases, including musculo-skeletal disorders. Fibrodysplasia ossificans progressiva (FOP) is a rare disorder characterized by progressive formation of ectopic bone and congenital malformations of the great toes. At present no curative therapy is available, therefore prevention of heterotopic ossification is the hallmark of FOP management. FOP has been linked to an autosomal dominant mutation on chromosome 2, to the gene encoding activin receptor-like kinase 2 (ALK2), a BMP type I receptor. This mutation is found in almost all classically affected FOP patients and causes the FOP phenotype. This discovery has paved the way for further investigations into the molecular basis underlying FOP and has recently pointed towards potential strategies to treat this devastating disease.
Export Options
About this article
Cite this article as:
J.J. de Gorter David, Jankipersadsing Vishant and ten Dijke Peter, Deregulated Bone Morphogenetic Protein Receptor Signaling Underlies Fibrodysplasia Ossificans Progressiva, Current Pharmaceutical Design 2012; 18 (27) . https://dx.doi.org/10.2174/138161212802430495
DOI https://dx.doi.org/10.2174/138161212802430495 |
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
-
AMPK As A Target in Rare Diseases
Current Drug Targets Epigenetic Effects of Cadmium in Cancer: Focus on Melanoma
Current Genomics Emerging Therapeutic Approaches Based on Nanotechnology for the Treatment of Diseases Associated with Telomere Dysfunction
Mini-Reviews in Medicinal Chemistry Pericyte: Potential Target for Hemorrhagic Stroke Prevention and Treatment
Current Drug Delivery Sonographic Diagnosis of Fetal Intraventricular Hemorrhage: Report of Three Cases and Review of the Literature
Recent Patents on Medical Imaging Cardiac Tissue Engineering
Recent Patents on Regenerative Medicine MicroRNA Regulation in Cardiovascular Disease
Current Drug Targets Novel Concepts in the Pathogenesis and Management of Pediatric Hypertension
Current Pediatric Reviews Low-Cost Infertility Management
Current Women`s Health Reviews Application of Dual-Source CT Coronary Angiography in Type 2 Diabetic Patients with Symptomatic Coronary Heart Disease
Current Vascular Pharmacology Connective Tissue Remodeling: Cross-Talk between Endothelins and Matrix Metalloproteinases
Current Vascular Pharmacology HspB5/αB-Crystallin: Properties and Current Progress in Neuropathy
Current Neurovascular Research Perspectives on Medicinal Properties of Benzoquinone Compounds
Mini-Reviews in Medicinal Chemistry Regulation of Intracellular Cardiomyocyte Calcium Stores by Peptides: A New Approach to Cardiac Protection
Current Medicinal Chemistry Low Estimated Glomerular Filtration Rate is Associated with High Recurrence Rate and Poor Prognosis of Hemorrhage Stroke
Current Neurovascular Research Therapeutic Potential of Natural Compounds that Regulate the Activity of Protein Kinase C
Current Medicinal Chemistry Future Challenges for Microsomal Transport Protein Inhibitors
Current Vascular Pharmacology Neonatal Germ Cell Tumors
Current Pediatric Reviews Anomalous Vascular Supply of Bronchial Circulation in Cystic Fibrosis Patients with Massive Hemoptysis
Current Respiratory Medicine Reviews A Pharmacological Primer of Biased Agonism
Endocrine, Metabolic & Immune Disorders - Drug Targets