Abstract
This mini review covers the drug discovery aspect of both proteasome activators and inhibitors. The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. Due to the importance of the proteasome in cellular functions, inhibition or activation of the proteasome could become a useful therapeutic strategy for a variety of diseases. Many proteasome inhibitors have been identified and can be classified into two groups according to their source: chemically synthesized small molecules and compounds derived from natural products. A successful example of development of a proteasome inhibitor as a clinically useful drug is the peptide boronate, PS341 (Bortezomib), was approved for the treatment of multiple myeloma. In contrast to proteasome inhibitors, small molecules that can activate or enhance proteasome activity are rare and are not well studied. The fact that overexpression of the cellular proteasome activator PA28 exhibited beneficial effects on the Huntingtons disease neuronal model cells raised the prospect that small molecule proteasome activators could become useful therapeutics. The beneficial effect of oleuropein, a small molecule proteasome activator, on senescence of human fibroblasts also suggested that proteasome activators might have the potential to be developed into anti-aging agents.
Keywords: Proteasome, activator, inhibitor, natural products, betulinic acids, peptides, anti-cancer, bortezomib
Current Medicinal Chemistry
Title: Proteasome Regulators: Activators and Inhibitors
Volume: 16 Issue: 8
Author(s): Li Huang and Chin Ho Chen
Affiliation:
Keywords: Proteasome, activator, inhibitor, natural products, betulinic acids, peptides, anti-cancer, bortezomib
Abstract: This mini review covers the drug discovery aspect of both proteasome activators and inhibitors. The proteasome is involved in many essential cellular functions, such as regulation of cell cycle, cell differentiation, signal transduction pathways, antigen processing for appropriate immune responses, stress signaling, inflammatory responses, and apoptosis. Due to the importance of the proteasome in cellular functions, inhibition or activation of the proteasome could become a useful therapeutic strategy for a variety of diseases. Many proteasome inhibitors have been identified and can be classified into two groups according to their source: chemically synthesized small molecules and compounds derived from natural products. A successful example of development of a proteasome inhibitor as a clinically useful drug is the peptide boronate, PS341 (Bortezomib), was approved for the treatment of multiple myeloma. In contrast to proteasome inhibitors, small molecules that can activate or enhance proteasome activity are rare and are not well studied. The fact that overexpression of the cellular proteasome activator PA28 exhibited beneficial effects on the Huntingtons disease neuronal model cells raised the prospect that small molecule proteasome activators could become useful therapeutics. The beneficial effect of oleuropein, a small molecule proteasome activator, on senescence of human fibroblasts also suggested that proteasome activators might have the potential to be developed into anti-aging agents.
Export Options
About this article
Cite this article as:
Huang Li and Chen Ho Chin, Proteasome Regulators: Activators and Inhibitors, Current Medicinal Chemistry 2009; 16 (8) . https://dx.doi.org/10.2174/092986709787581860
DOI https://dx.doi.org/10.2174/092986709787581860 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Multi- and Inter-Disciplinary Science in Personalized Delivery of Stem Cells for Tissue Repair
Current Stem Cell Research & Therapy Harnessing the Natural Pool of Polyketide and Non-ribosomal Peptide Family: A Route Map towards Novel Drug Development
Current Molecular Pharmacology Sphingolipids as Emerging Drug Targets: Therapeutic Applications of Ceramide Analogs
Drug Design Reviews - Online (Discontinued) Mitochondrial Drug Targets in Cell Death and Cancer
Current Pharmaceutical Design Prion Disease: Chemotherapeutic Strategies
Infectious Disorders - Drug Targets Inhibition of Hypusine Biosynthesis in Plasmodium: A Possible, New Strategy in Prevention and Therapy of Malaria
Mini-Reviews in Medicinal Chemistry Apoptosis-related BCL2-family Members: Key Players in Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry A beta oligomerization A Therapeutic Target for Alzheimers Disease
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Regulation of Gait and Balance: The Underappreciated Role of Neuronal Nicotinic Receptor Agonists
Current Pharmaceutical Design How is Gene Transfection Able to Improve Current Chemotherapy? The Role of Combined Therapy in Cancer Treatment
Current Medicinal Chemistry The Contribution of Buckwheat Genetic Resources to Health and Dietary Diversity
Current Genomics The Cell Cycle and Hormonal Fluxes in Alzheimer Disease: A Novel Therapeutic Target
Current Pharmaceutical Design Oxysterol Derivatives of Cholesterol in Neurodegenerative Disorders
Current Medicinal Chemistry Tumour Reactions to Hypoxia
Current Molecular Medicine Evaluation of Dendrimer Safety and Efficacy through Cell Line Studies
Current Drug Targets The Role of NF-κB Inhibitors in Cell Response to Radiation
Current Medicinal Chemistry Delivery Systems for Birch-bark Triterpenoids and their Derivatives in Anticancer Research
Current Medicinal Chemistry Pathobiology and Prevention of Cancer Chemotherapy-Induced Bone Growth Arrest, Bone Loss, and Osteonecrosis
Current Molecular Medicine Decision Support System for Lymphoma Classification
Current Medical Imaging Gamma-Secretase as a Pharmacological Target in Alzheimer Disease Research: When, Why and How?
Current Pharmaceutical Design