Abstract
The recognition that malfunction of the microtubule (MT) associated protein tau is likely to play a defining role in the onset and/or progression of a number of neurodegenerative diseases, including Alzheimers disease, has resulted in the initiation of drug discovery programs that target this protein. Tau is an endogenous MT-stabilizing agent that is highly expressed in the axons of neurons. The MT-stabilizing function of tau is essential for the axonal transport of proteins, neurotransmitters and other cellular constituents. Under pathological conditions, tau misfolding and aggregation results in axonal transport deficits that appear to have deleterious consequences for the affected neurons, leading to synapse dysfunction and, ultimately, neuronal loss. This review focuses on both progress and unresolved issues surrounding the development of novel therapeutics for the treatment of neurodegenerative tauopathies, which are based on (A) MT-stabilizing agents to compensate for the loss of normal tau function and (B) small molecule inhibitors of tau aggregation.
Keywords: Protein-protein interaction, tau, Alzheimer's disease, neurodegenerative tauopathies, microtubule-stabilizing agents, aggregation inhibitors, microtubule, neuronal loss, cyclosporine A, FK506, taxanes, vinca alkaloids, RGD-mimetics, central nervous system, Pick's disease, frontotemporal dementia, neurofibrillary tangles, frontotemporal lobar degeneration, tau-MT complex, phosphorylation, antineoplastic agents, rheumatoid arthritis, psoriasis, paclitaxel, blood-brain barrier, P-glycoprotein, ATP-binding cassette, IDN5109, brain to plasma ratio, TXD258, Larotaxel, ANG1005, Angiopep-2, Epothilones, Ixabepilone, desoxyepothilones, discodermolide, dictyostatin, cyclostreptin, davunetide, N-methyl-D-aspartate, phenothiazines, anthraquinones, N-phenylamines, thiazolyl-hydrazides, rhodanines, quinoxalines, aminothienopyridazines
Current Topics in Medicinal Chemistry
Title: Modulation of Protein-Protein Interactions as a Therapeutic Strategy for the Treatment of Neurodegenerative Tauopathies
Volume: 11 Issue: 3
Author(s): C. Ballatore, K. R. Brunden, J. Q. Trojanowski, V. M.-Y. Lee, A. B. Smith and D. M. Huryn
Affiliation:
Keywords: Protein-protein interaction, tau, Alzheimer's disease, neurodegenerative tauopathies, microtubule-stabilizing agents, aggregation inhibitors, microtubule, neuronal loss, cyclosporine A, FK506, taxanes, vinca alkaloids, RGD-mimetics, central nervous system, Pick's disease, frontotemporal dementia, neurofibrillary tangles, frontotemporal lobar degeneration, tau-MT complex, phosphorylation, antineoplastic agents, rheumatoid arthritis, psoriasis, paclitaxel, blood-brain barrier, P-glycoprotein, ATP-binding cassette, IDN5109, brain to plasma ratio, TXD258, Larotaxel, ANG1005, Angiopep-2, Epothilones, Ixabepilone, desoxyepothilones, discodermolide, dictyostatin, cyclostreptin, davunetide, N-methyl-D-aspartate, phenothiazines, anthraquinones, N-phenylamines, thiazolyl-hydrazides, rhodanines, quinoxalines, aminothienopyridazines
Abstract: The recognition that malfunction of the microtubule (MT) associated protein tau is likely to play a defining role in the onset and/or progression of a number of neurodegenerative diseases, including Alzheimers disease, has resulted in the initiation of drug discovery programs that target this protein. Tau is an endogenous MT-stabilizing agent that is highly expressed in the axons of neurons. The MT-stabilizing function of tau is essential for the axonal transport of proteins, neurotransmitters and other cellular constituents. Under pathological conditions, tau misfolding and aggregation results in axonal transport deficits that appear to have deleterious consequences for the affected neurons, leading to synapse dysfunction and, ultimately, neuronal loss. This review focuses on both progress and unresolved issues surrounding the development of novel therapeutics for the treatment of neurodegenerative tauopathies, which are based on (A) MT-stabilizing agents to compensate for the loss of normal tau function and (B) small molecule inhibitors of tau aggregation.
Export Options
About this article
Cite this article as:
Ballatore C., R. Brunden K., Q. Trojanowski J., M.-Y. Lee V., B. Smith A. and M. Huryn D., Modulation of Protein-Protein Interactions as a Therapeutic Strategy for the Treatment of Neurodegenerative Tauopathies, Current Topics in Medicinal Chemistry 2011; 11 (3) . https://dx.doi.org/10.2174/156802611794072605
DOI https://dx.doi.org/10.2174/156802611794072605 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as Co-Ligands
Current Radiopharmaceuticals Anti-Angiogenic Peptides for Cancer Therapeutics
Current Pharmaceutical Biotechnology Serum Carboxypeptidase N1 Serves as a Potential Biomarker Complementing CA15-3 for Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry TRAIL Agonists on Clinical Trials for Cancer Therapy: The Promises and the Challenges
Reviews on Recent Clinical Trials Cancer Stem Cells: A New Paradigm for Understanding Tumor Growth and Progression and Drug Resistance
Current Medicinal Chemistry Liposome-Encapsulated Photosensitizers Against Bacteria
Recent Patents on Anti-Infective Drug Discovery Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine
Current Genomics Manganese Superoxide Dismutase (Sod2) and Redox-Control of Signaling Events That Drive Metastasis
Anti-Cancer Agents in Medicinal Chemistry Tamoxifen and its New Derivatives in Cancer Research
Recent Patents on Anti-Cancer Drug Discovery Serum miRNAs Signature Plays an Important Role in Keloid Disease
Current Molecular Medicine Redox-active and Redox-silent Compounds: Synergistic Therapeutics in Cancer
Current Medicinal Chemistry Recent Progress in Polynuclear Ruthenium Complex-Based DNA Binders/Structural Probes and Anticancer Agents
Current Medicinal Chemistry 19F: A Versatile Reporter for Non-Invasive Physiology and Pharmacology Using Magnetic Resonance
Current Medicinal Chemistry A hypothesis for the role of RECK in angiogenesis
Current Vascular Pharmacology Chronic Inflammation and Colorectal Cancer: The Role of Vascular Endothelial Growth Factor
Current Pharmaceutical Design Doxycycline as Potential Anti-cancer Agent
Anti-Cancer Agents in Medicinal Chemistry Reconceptualizing Adult Neurogenesis: Role for Sphingosine-1-Phosphate and Fibroblast Growth Factor-1 in Co-Ordinating Astrocyte-Neuronal Precursor Interactions
CNS & Neurological Disorders - Drug Targets Breaking the Barrier of Cancer Through Liposome Loaded with Phytochemicals
Current Drug Delivery Influence of Enzyme-Inducing Antiepileptic Drugs on Trough Level of Imatinib in Glioblastoma Patients
Current Clinical Pharmacology Natural Bio-Drugs as Matrix Metalloproteinase Inhibitors: New Perspectives on the Horizon?
Recent Patents on Anti-Cancer Drug Discovery