Abstract
The general view on cysteine cathepsins, which were long believed to be primarily involved in intracellular protein turnover, has dramatically changed in last 10 to 15 years. The discovery of new cathepsins, such as cathepsins K, V, X, F and O, and their tissue distribution suggested that at least some of them are involved in very specific cellular processes. Moreover, gene ablation experiments revealed that cathepsins play a vital role in numerous physiological processes, such as antigen processing and presentation, bone remodelling, prohormone processing and wound healing. Their involvement in several pathologies, including osteoporosis, rheumatoid arthritis, osteoarthritis, bronchial asthma and cancer have also been confirmed and today several of them have been validated as relevant targets for therapies. Compounds targeting cathepsins S and K are already in clinical evaluation, whereas others are in experimental phases. The cathepsin K inhibitor AAE-581 (balicatib) as the most advanced of them passed Phase II clinical trials in 2005. In this review, we discuss the current view on cathepsins as an emerging group of targets for several diseases and the development of cathepsin K and S inhibitors for treatment of osteoporosis and various immune disorders.
Keywords: Carboxypeptidases cathepsins B, Apoptosis, cancer biology, Tumour Angiogenesis, extracellular matrix (ECM), MHC Class II Antigen
Current Pharmaceutical Design
Title: Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets
Volume: 13 Issue: 4
Author(s): Olga Vasiljeva, Thomas Reinheckel, Christoph Peters, Dusan Turk, Vito Turk and Boris Turk
Affiliation:
Keywords: Carboxypeptidases cathepsins B, Apoptosis, cancer biology, Tumour Angiogenesis, extracellular matrix (ECM), MHC Class II Antigen
Abstract: The general view on cysteine cathepsins, which were long believed to be primarily involved in intracellular protein turnover, has dramatically changed in last 10 to 15 years. The discovery of new cathepsins, such as cathepsins K, V, X, F and O, and their tissue distribution suggested that at least some of them are involved in very specific cellular processes. Moreover, gene ablation experiments revealed that cathepsins play a vital role in numerous physiological processes, such as antigen processing and presentation, bone remodelling, prohormone processing and wound healing. Their involvement in several pathologies, including osteoporosis, rheumatoid arthritis, osteoarthritis, bronchial asthma and cancer have also been confirmed and today several of them have been validated as relevant targets for therapies. Compounds targeting cathepsins S and K are already in clinical evaluation, whereas others are in experimental phases. The cathepsin K inhibitor AAE-581 (balicatib) as the most advanced of them passed Phase II clinical trials in 2005. In this review, we discuss the current view on cathepsins as an emerging group of targets for several diseases and the development of cathepsin K and S inhibitors for treatment of osteoporosis and various immune disorders.
Export Options
About this article
Cite this article as:
Vasiljeva Olga, Reinheckel Thomas, Peters Christoph, Turk Dusan, Turk Vito and Turk Boris, Emerging Roles of Cysteine Cathepsins in Disease and their Potential as Drug Targets, Current Pharmaceutical Design 2007; 13 (4) . https://dx.doi.org/10.2174/138161207780162962
DOI https://dx.doi.org/10.2174/138161207780162962 |
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
-
Association Between Hypothyroidism and Takotsubo Cardiomyopathy: Analysis of Nationwide Inpatient Sample Database
Reviews on Recent Clinical Trials Berberine: New Insights from Pharmacological Aspects to Clinical Evidences in the Management of Metabolic Disorders
Current Medicinal Chemistry The Therapeutic Potential of Bone Marrow Mesenchymal Stem Cells for Articular Cartilage Regeneration in Osteoarthritis
Current Stem Cell Research & Therapy Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Heart Failure in Sub-Saharan Africa
Current Cardiology Reviews Cardiac Nuclear Imaging: Current Status and Future Directions
Current Medical Imaging CD147 Interacts with NDUFS6 in Regulating Mitochondrial Complex I Activity and the Mitochondrial Apoptotic Pathway in Human Malignant Melanoma Cells
Current Molecular Medicine AMPK As A Target in Rare Diseases
Current Drug Targets Editorial (Thematic Issue: Mechanistic Biomarkers: The Field for the Development of Non-Pharmaceutical and Pharmaceutical Approaches to Diagnostics, Prevention and Treatment of Chronic Diseases)
Current Pharmaceutical Design Pharmacologically Targeting the Primary Defect and Downstream Pathology in Duchenne Muscular Dystrophy
Current Gene Therapy The Evolving Therapy of Rheumatic Diseases, The Future is Now
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Editorial (Thematic Issue: Current Topics in Pharmacogenomics)
Recent Patents on Biotechnology Cardiac Side Effects of Chemotherapy: State of Art and Strategies for a Correct Management
Current Vascular Pharmacology Heart Disease in Patients with HIV/AIDS-An Emerging Clinical Problem
Current Cardiology Reviews Fabry Disease Cardiomyopathy: from Genes to Clinical Manifestations
Current Pharmaceutical Biotechnology Prevention of Left Ventricular Remodelling after Acute Myocardial Infarction: An Update
Recent Patents on Cardiovascular Drug Discovery Role of PI3K/AKT/mTOR Pathway Associated Oxidative Stress and Cardiac Dysfunction in Takotsubo Syndrome
Current Neurovascular Research EDITORIAL [Hot Topic: Diabetes Cardiovascular Complications (Guest Editor: Costanza Emanueli)]
Endocrine, Metabolic & Immune Disorders - Drug Targets Genomic Databases and the Search of Protein Targets for Protozoan Parasites
Current Drug Targets Preclinical Development of New Therapy for Glycogen Storage Diseases
Current Gene Therapy