Abstract
Neurodegenerative diseases characterized by the accumulation of tau aggregates are increasing in prevalence to epidemic-like levels and there is currently no effective treatment. For many years, the focus of tau-based research was on the fibrillar, neurofibrillary tangles. However, the compilation of evidence obtained from numerous laboratories in the past few years suggests that soluble intermediate aggregates—tau oligomers—are actually the most toxic protein species in disease. Thus, therapeutic agents that target oligomeric tau specifically may be the most effective routes for treatment. A great deal of progress has been made in the pre-clinical evaluation of a number of different anti-tau therapeutics. Upstream modulators of tau modifications have been evaluated and may provide some benefits, but likely will not be capable of eliminating toxic tau entirely. Protein chaperones capable of modulating the structure of tau and targeting it for degradation are another field of study, however, the broad effects of chaperones make side effects a concern. Thus, more specific agents capable of eliminating the most toxic species in disease are promising. Small molecules designed to inhibit aggregation, as well as immunotherapy with antibodies specific for toxic tau aggregates present the most advancement as potential treatments. The concerted effort across a number of groups to investigate potential mechanisms to inhibit tau toxicity represents great progress in the field and provides hope that effective treatments will be discovered.
Keywords: Tau aggregation, tau oligomers, pathological tau, small molecules, immunotherapy.
Current Pharmaceutical Design
Title:Therapeutic Approaches Targeting Pathological Tau Aggregates
Volume: 22 Issue: 26
Author(s): Julia Gerson and Rakez Kayed
Affiliation:
Keywords: Tau aggregation, tau oligomers, pathological tau, small molecules, immunotherapy.
Abstract: Neurodegenerative diseases characterized by the accumulation of tau aggregates are increasing in prevalence to epidemic-like levels and there is currently no effective treatment. For many years, the focus of tau-based research was on the fibrillar, neurofibrillary tangles. However, the compilation of evidence obtained from numerous laboratories in the past few years suggests that soluble intermediate aggregates—tau oligomers—are actually the most toxic protein species in disease. Thus, therapeutic agents that target oligomeric tau specifically may be the most effective routes for treatment. A great deal of progress has been made in the pre-clinical evaluation of a number of different anti-tau therapeutics. Upstream modulators of tau modifications have been evaluated and may provide some benefits, but likely will not be capable of eliminating toxic tau entirely. Protein chaperones capable of modulating the structure of tau and targeting it for degradation are another field of study, however, the broad effects of chaperones make side effects a concern. Thus, more specific agents capable of eliminating the most toxic species in disease are promising. Small molecules designed to inhibit aggregation, as well as immunotherapy with antibodies specific for toxic tau aggregates present the most advancement as potential treatments. The concerted effort across a number of groups to investigate potential mechanisms to inhibit tau toxicity represents great progress in the field and provides hope that effective treatments will be discovered.
Export Options
About this article
Cite this article as:
Gerson Julia and Kayed Rakez, Therapeutic Approaches Targeting Pathological Tau Aggregates, Current Pharmaceutical Design 2016; 22 (26) . https://dx.doi.org/10.2174/1381612822666160518142226
DOI https://dx.doi.org/10.2174/1381612822666160518142226 |
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
-
Chemokine Receptor CCR5 Antagonist Maraviroc: Medicinal Chemistry and Clinical Applications
Current Topics in Medicinal Chemistry Coinhibitory Molecule PD-1 as a Therapeutic Target in the Microenvironment of Multiple Myeloma
Current Cancer Drug Targets Bone Marrow Stem Cell Therapy for Myocardial Angiogenesis
Current Vascular Pharmacology Angiotensin-Converting Enzyme Inhibitors: Mechanisms of Action and Implications In Anesthesia Practice
Current Pharmaceutical Design Chebulagic Acid Synergizes the Cytotoxicity of Doxorubicin in Human Hepatocellular Carcinoma Through COX-2 Dependant Modulation of MDR-1
Medicinal Chemistry Gemcitabine-Related Atrial Fibrillation: A Case Report and Review of the Literature
Current Drug Safety Autoimmunity and Celiac Disease
Mini-Reviews in Medicinal Chemistry ROS Acts as a Double-Edged Sword in the Pathogenesis of Type 2 Diabetes Mellitus: Is Nrf2 a Potential Target for the Treatment?
Mini-Reviews in Medicinal Chemistry The Fetal Cardiac Function
Current Cardiology Reviews Utility of Anti-Arrhythmic Medications in ‘Lone Atrial Fibrillation’
Current Pharmaceutical Design Application of Resveratrol in Diabetes: Rationale, Strategies and Challenges
Current Molecular Medicine Multidrug Resistance Associated Proteins as Determining Factors of Pharmacokinetics and Pharmacodynamics of Drugs
Current Drug Metabolism The Delivery of Personalised, Precision Medicines <i>via</i> Synthetic Proteins
Drug Delivery Letters Non-glycemic Adverse Effects of Insulin
Current Diabetes Reviews Editorial (Thematic Issue: Mechanistic Biomarkers: The Field for the Development of Non-Pharmaceutical and Pharmaceutical Approaches to Diagnostics, Prevention and Treatment of Chronic Diseases)
Current Pharmaceutical Design Dysregulation of Glycogen Synthase Kinase-3 in Skeletal Muscle and the Etiology of Insulin Resistance and Type 2 Diabetes
Current Diabetes Reviews Platelets in Atherothrombosis - Diagnostic and Prognostic Value of Platelet Activation in Patients with Atherosclerotic Diseases
Current Vascular Pharmacology Combined Anticancer Therapies: An Overview of the Latest Applications
Anti-Cancer Agents in Medicinal Chemistry Proinflammatory Gene Polymorphisms and Ischemic Stroke
Current Pharmaceutical Design Reducing the Risk of Major Elective Non-cardiac Surgery: Is there a Role for Levosimendan in the Preoperative Optimization of Cardiac Function?
Current Drug Targets