Abstract
Protein misfolding has been implicated in the pathophysiology of several neurodegenerative ‘amyloidoses’ that includes Alzheimers, Parkinsons, Huntingtons disease, frontotemporal dementia and amyotrophic lateral sclerosis. Accumulation of misfolded proteins into ordered fibrillar intra- or extracellular amyloids results in brain lesions that in turn lead to injury and neuronal loss. The appearance of protein aggregates in the diseased brain hints at an inability of cellular chaperones to properly assist folding of client proteins. Not surprisingly, studies involving cell-based and animal models of the neurodegenerative diseases have shown that overexpression of molecular chaperones can provide neuroprotection. Together with identification of new targets for symptomatic relief of motor and non-motor defects in neurodegenerative disorders, there is a critical unmet clinical need for the development of novel neuroprotective molecules. One such promising class of compounds are neuroimmunophilin ligands (NILs). Derived from FK506 (tacrolimus), NILs have been shown to be efficacious in a number of neurodegenerative disorders. The ability of these nonimmunosuppressive NILs to protect neurons is modulated, in part, by a large family of co-chaperone proteins called the FK506 binding proteins (FKBPs). This review focuses on the roles of FKBPs in neurodegenerative disorders with an emphasis on the cellular mechanisms responsible for their neuroprotective and neurotrophic activities. We discuss the structural features of FKBPs and the mode of action of NILs. For brevity, we limit our discussion to those FKBPs that are particularly enriched in the nervous system. We hope that such information will aid in the rational design of new and improved NILs for ameliorating neurodegenerative disorders.
Keywords: FK506 binding proteins FKBPs), neurodegenerative disorders, FK506 (Tacrolimus), PPIase activity, neuroimmunophilin ligand, pathophysiology, amyloidoses, frontotemporal dementia, amyotrophic lateral sclerosis, misfolded proteins, neuroimmunophilin ligand (NIL)
Current Medicinal Chemistry
Title: Role of FK506 Binding Proteins in Neurodegenerative Disorders
Volume: 18 Issue: 35
Author(s): S. Chattopadhaya, A. Harikishore and H. S. Yoon
Affiliation:
Keywords: FK506 binding proteins FKBPs), neurodegenerative disorders, FK506 (Tacrolimus), PPIase activity, neuroimmunophilin ligand, pathophysiology, amyloidoses, frontotemporal dementia, amyotrophic lateral sclerosis, misfolded proteins, neuroimmunophilin ligand (NIL)
Abstract: Protein misfolding has been implicated in the pathophysiology of several neurodegenerative ‘amyloidoses’ that includes Alzheimers, Parkinsons, Huntingtons disease, frontotemporal dementia and amyotrophic lateral sclerosis. Accumulation of misfolded proteins into ordered fibrillar intra- or extracellular amyloids results in brain lesions that in turn lead to injury and neuronal loss. The appearance of protein aggregates in the diseased brain hints at an inability of cellular chaperones to properly assist folding of client proteins. Not surprisingly, studies involving cell-based and animal models of the neurodegenerative diseases have shown that overexpression of molecular chaperones can provide neuroprotection. Together with identification of new targets for symptomatic relief of motor and non-motor defects in neurodegenerative disorders, there is a critical unmet clinical need for the development of novel neuroprotective molecules. One such promising class of compounds are neuroimmunophilin ligands (NILs). Derived from FK506 (tacrolimus), NILs have been shown to be efficacious in a number of neurodegenerative disorders. The ability of these nonimmunosuppressive NILs to protect neurons is modulated, in part, by a large family of co-chaperone proteins called the FK506 binding proteins (FKBPs). This review focuses on the roles of FKBPs in neurodegenerative disorders with an emphasis on the cellular mechanisms responsible for their neuroprotective and neurotrophic activities. We discuss the structural features of FKBPs and the mode of action of NILs. For brevity, we limit our discussion to those FKBPs that are particularly enriched in the nervous system. We hope that such information will aid in the rational design of new and improved NILs for ameliorating neurodegenerative disorders.
Export Options
About this article
Cite this article as:
Chattopadhaya S., Harikishore A. and S. Yoon H., Role of FK506 Binding Proteins in Neurodegenerative Disorders, Current Medicinal Chemistry 2011; 18 (35) . https://dx.doi.org/10.2174/092986711798194441
DOI https://dx.doi.org/10.2174/092986711798194441 |
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
-
Drug Delivery Technologies and Stem Cells for Tissue Repair and Regeneration
Current Pharmaceutical Biotechnology Intrinsically Disordered Domains, Amyloids and Protein Liquid Phases: Evolving Concepts and Open Questions
Protein & Peptide Letters Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Anti-neoplastic and Calcium modulatory action of Caffeic acid phenethyl ester and Dasatinib in C6 glial cells: A Therapeutic Perspective
CNS & Neurological Disorders - Drug Targets Emerging Perspectives on DNA Double-strand Breaks in Neurodegenerative Diseases
Current Neuropharmacology Editorial (Hot Topic: Network Biology: Towards Systematic Understanding of Biological Systems)
Current Bioinformatics A Role for TGF-β Signaling in Neurodegeneration: Evidence from Genetically Engineered Models
Current Alzheimer Research Subject Index To Volume 3
Current Alzheimer Research Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review
Current Pharmaceutical Design Targeting Microglial Activation in Stroke Therapy: Pharmacological Tools and Gender Effects
Current Medicinal Chemistry Drug Repositioning for Treatment of Movement Disorders: From Serendipity to Rational Discovery Strategies
Current Topics in Medicinal Chemistry Micro Arrays and Biochips: Applications and Potential in Genomics and Proteomics
Current Genomics Genistein: A Phytoestrogen with Multifaceted Therapeutic Properties
Mini-Reviews in Medicinal Chemistry Interaction of Dehydrogenase Enzymes with Nanoparticles in Industrial and Medical Applications, and the Associated Challenges: A Mini-review
Mini-Reviews in Medicinal Chemistry Targeting Hsp90 in Non-Cancerous Maladies
Current Topics in Medicinal Chemistry Editorial [Hot Topic: Sigma Receptor Research: Progress Towards Diagnostic and Therapeutic Uses of Sigma Ligands (Executive Guest Editor: Carmen Abate )]
Current Pharmaceutical Design Disease-Modifying Therapies in Frontotemporal Lobar Degeneration
Current Medicinal Chemistry RNAi for the Treatment of Prion Disease: A Window for Intervention in Neurodegeneration?
CNS & Neurological Disorders - Drug Targets Monitoring the Inflammatory Process by Surface Enhanced Nanoimaging Microscopy
Current Neurovascular Research Therapeutic Approaches for Lysosomal Storage Diseases: A Patent Update
Recent Patents on CNS Drug Discovery (Discontinued)