Abstract
The intracellular cysteine proteinases grouped under the common name of caspases are important participants in the process of programmed cell death called apoptosis. Of the nearly fourteen mammalian members discovered thus far caspase 1 or (interleukin-1β converting enzyme ICE), and possibly other related family members also serve as activator of cytokines. In general, caspases act on a number of cellular targets including other caspase family members leading ultimately to apopto4 4is through a highly integrated and regulated biological, biochemical and genetic mechanism. The proper execution of apoptosis is crucial during developmental stages and continues to be of critical importance for the well being of the mature organism. However, in a number of degenerative diseases the pathological states are characterized by an exacerbated loss of certain types of cells, cellular death that has morphological characteristics of apoptosis. Fortunately, it has been known for sometime that induced apoptosis that proceeds through the activation of caspases can be inhibited to rescue these cells and allow them to remain viable. This realization has attracted attention towards caspases as likely targets for pharmacological intervention, believing that inhibition of their enzymatic activity in the compromised cells will prevent the unwanted high rate of cellular death. Here we survey natural and synthetic inhibitors of caspases that have been reported to date, including some commonly used peptide inhibitors that serve as ”tool reagents“ in research and others that have been used to map inhibitor binding interaction in the active site.
Keywords: Apoptosis, Caenorhabditis elegans, Huntingtons disease, Peptide Inhibitors, benzamidomethyl ketone, Isatin Sulfonamide Inhibitors
Current Medicinal Chemistry
Title: Controlling Apoptosis by Inhibition of Caspases
Volume: 9 Issue: 6
Author(s): N. O. Concha and S. S. Abdel-Meguid
Affiliation:
Keywords: Apoptosis, Caenorhabditis elegans, Huntingtons disease, Peptide Inhibitors, benzamidomethyl ketone, Isatin Sulfonamide Inhibitors
Abstract: The intracellular cysteine proteinases grouped under the common name of caspases are important participants in the process of programmed cell death called apoptosis. Of the nearly fourteen mammalian members discovered thus far caspase 1 or (interleukin-1β converting enzyme ICE), and possibly other related family members also serve as activator of cytokines. In general, caspases act on a number of cellular targets including other caspase family members leading ultimately to apopto4 4is through a highly integrated and regulated biological, biochemical and genetic mechanism. The proper execution of apoptosis is crucial during developmental stages and continues to be of critical importance for the well being of the mature organism. However, in a number of degenerative diseases the pathological states are characterized by an exacerbated loss of certain types of cells, cellular death that has morphological characteristics of apoptosis. Fortunately, it has been known for sometime that induced apoptosis that proceeds through the activation of caspases can be inhibited to rescue these cells and allow them to remain viable. This realization has attracted attention towards caspases as likely targets for pharmacological intervention, believing that inhibition of their enzymatic activity in the compromised cells will prevent the unwanted high rate of cellular death. Here we survey natural and synthetic inhibitors of caspases that have been reported to date, including some commonly used peptide inhibitors that serve as ”tool reagents“ in research and others that have been used to map inhibitor binding interaction in the active site.
Export Options
About this article
Cite this article as:
Concha O. N. and Abdel-Meguid S. S., Controlling Apoptosis by Inhibition of Caspases, Current Medicinal Chemistry 2002; 9 (6) . https://dx.doi.org/10.2174/0929867023370761
DOI https://dx.doi.org/10.2174/0929867023370761 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Endothelial Dysfunction in Morbid Obesity
Current Pharmaceutical Design Angiogenesis as Risk Factor for Plaque Vulnerability
Current Pharmaceutical Design Cardiovascular Diseases and the Nitric Oxide Pathway
Current Vascular Pharmacology Neuroinflammation, Microglia and Mast Cells in the Pathophysiology of Neurocognitive Disorders: A Review
CNS & Neurological Disorders - Drug Targets The Histamine H3 Receptor as a Therapeutic Drug Target for Metabolic Disorders: Status, Challenges and Opportunities
Current Topics in Medicinal Chemistry Biochemical Markers for Brain Injury Monitoring in Children with or without Congenital Heart Diseases
CNS & Neurological Disorders - Drug Targets Heart Failure Models: Traditional and Novel Therapy
Current Vascular Pharmacology The Biological Potentials of Indian Traditional Medicine, Curcumin for Treating Human Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Melatonin as Antioxidant Under Pathological Processes
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Selection of Antithrombotic Therapy in Patients with Atrial Fibrillation and Percutaneous Coronary Intervention
Current Pharmaceutical Design To Be-et, or Not to Be-et, That is the Question: The Role(s) of Nitrate and Nitrite in Health and Illness
Reviews on Recent Clinical Trials Highlighting Exosomes’ Function in Cardiovascular Diseases
Current Cardiology Reviews Cell-Based Therapy to Promote Angiogenesis in the Brain Following Ischemic Damage
Current Vascular Pharmacology Relationship Between Cigarette Smoking and Other Coronary Risk Factors in Atherosclerosis: Risk of Cardiovascular Disease and Preventive Measures
Current Pharmaceutical Design Anti-Vascular Endothelial Growth Factor (VEGF) Therapy: A New Cause of Hypertension
Current Hypertension Reviews Beta Blocker Use After Acute Myocardial Infarction in the Patient with Normal Systolic Function: When is it “Ok” to Discontinue?
Current Cardiology Reviews Epidemiology and Costs of Hypertension-related Disorders
Current Pharmaceutical Design Oral Antiplatelet Therapy for Acute Coronary Syndromes: Aspirin, P2Y12 Inhibition and Thrombin Receptor Antagonists
Current Drug Targets Reviewing the Cardiovascular Complications of HIV Infection After the Introduction of Highly Active Antiretroviral Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Calreticulin in the Heart: From Embryological Development to Cardiac Pathology.
Current Molecular Medicine