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
-
Recent Patents on Cardiovascular Stem Cells
Recent Patents on Cardiovascular Drug Discovery Biomarkers of Atrial Fibrillation in Hypertension
Current Medicinal Chemistry Perinatal Exposure to Bisphenol A and Developmental Programming of the Cardiovascular Changes in the Offspring
Current Medicinal Chemistry Editorial (Thematic Issue: Current Topics in Pharmacogenomics)
Recent Patents on Biotechnology T Lymphocytes as Targets of Statins: Molecular Mechanisms and Therapeutic Perspectives
Inflammation & Allergy - Drug Targets (Discontinued) Toxics of Tobacco Smoke and Cardiovascular System: From Functional to Cellular Damage
Current Pharmaceutical Design ErbB4 and its Isoforms: Patentable Drug Targets?
Recent Patents on DNA & Gene Sequences Withdrawal Notice: Therapeutic Options for Treatment of COVID-19: A Review from Repurposed Drugs to New Drug Targets
Current Drug Targets Editorial: (New Drug (LCZ696) for the Treatment of Heart Failure with Reduced Ejection Fraction After 10 Years. Can One Study Change the Guidelines?)
Current Vascular Pharmacology Sacubitril/Valsartan: A New Dawn has Begun! A Revisited Review
Current Cardiology Reviews Annexin A5 Imaging: An Academic Research – Clinical Trials and Theses
Current Molecular Imaging (Discontinued) What Does a Pediatrician Need to Know About Chronic Diarrhea?
Current Pediatric Reviews Puerarin: A Review on the Pharmacological Activity, Chemical Properties and Pharmacokinetics of Main Isoflavonoid
The Natural Products Journal Anti Diabetic Evaluation of Methanolic Extract of <i>Psoralea corylifolia</i> L. & <i>Psoralea esculenta</i> L. Seeds in Streptozotocin Induced Diabetic Rats and Histopathological Changes in Diabetic Rats Pancreas: A Comparative Study
The Natural Products Journal The gp130 Receptor Cytokine Family: Regulators of Adipocyte Development and Function
Current Pharmaceutical Design Heat Shock Protein-60 and Risk for Cardiovascular Disease
Current Pharmaceutical Design Targeting the EGFR-family for Therapy: Biological Challenges and Clinical Perspective
Current Pharmaceutical Design New Therapeutic Applications of Phosphodiesterase 5 Inhibitors (PDE5-Is)
Current Medicinal Chemistry Ghrelin and Cardiovascular Diseases
Current Cardiology Reviews CYLD-Mediated Signaling and Diseases
Current Drug Targets