Abstract
Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer’s disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer’s disease.
Keywords: Tau truncation; Alzheimer’s disease; neurofibrillary degeneration; tau transition.
Current Alzheimer Research
Title:Tau Truncation is a Productive Posttranslational Modification of Neurofibrillary Degeneration in Alzheimer’s Disease
Volume: 7 Issue: 8
Author(s): B. Kovacech and M. Novak
Affiliation:
Keywords: Tau truncation; Alzheimer’s disease; neurofibrillary degeneration; tau transition.
Abstract: Deposits of the misfolded neuronal protein tau are major hallmarks of neurodegeneration in Alzheimer’s disease (AD) and other tauopathies. The etiology of the transformation process of the intrinsically disordered soluble protein tau into the insoluble misordered aggregate has attracted much attention. Tau undergoes multiple modifications in AD, most notably hyperphosphorylation and truncation. Hyperphosphorylation is widely regarded as the hottest candidate for the inducer of the neurofibrillary pathology. However, the true nature of the impetus that initiates the whole process in the human brains remains unknown. In AD, several site-specific tau cleavages were identified and became connected to the progression of the disease. In addition, western blot analyses of tau species in AD brains reveal multitudes of various truncated forms. In this review we summarize evidence showing that tau truncation alone is sufficient to induce the complete cascade of neurofibrillary pathology, including hyperphosphorylation and accumulation of misfolded insoluble forms of tau. Therefore, proteolytical abnormalities in the stressed neurons and production of aberrant tau cleavage products deserve closer attention and should be considered as early therapeutic targets for Alzheimer’s disease.
Export Options
About this article
Cite this article as:
Kovacech B. and Novak M., Tau Truncation is a Productive Posttranslational Modification of Neurofibrillary Degeneration in Alzheimer’s Disease, Current Alzheimer Research 2010; 7 (8) . https://dx.doi.org/10.2174/156720510793611556
DOI https://dx.doi.org/10.2174/156720510793611556 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...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
-
Neurodegeneration with Dementia: From Fundamentals of Pathology to Clinical Imaging by MRI and SPECT.
Current Medical Imaging Antioxidant Capacities of Flavones and Benefits in Oxidative-Stress Related Diseases
Current Topics in Medicinal Chemistry The Effect of a Four-Week Balance Training Program on Anticipatory Postural Adjustments in Older Adults: A Pilot Feasibility Study
Current Aging Science Atypical Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children: A Systematic Review
Current Pediatric Reviews Effects of PPARγ Ligands on Vascular Tone
Current Molecular Pharmacology Neuronal and Glial Responses to Polyamines in the Ischemic Brain
Current Neurovascular Research Pharmacological Approach of No-Reflow Phenomenon Related with Percutaneous Coronary Interventions
Cardiovascular & Hematological Agents in Medicinal Chemistry Erythropoietin in Heart Failure and Other Cardiovascular Diseases: Hematopoietic and Pleiotropic Effects
Current Drug Targets - Cardiovascular & Hematological Disorders Cyclic Nucleotide Phosphodiesterases (PDE) and Peptide Motifs
Current Pharmaceutical Design Enkephalin-Fentanyl Multifunctional Opioids as Potential Neuroprotectants for Ischemic Stroke Treatment
Current Pharmaceutical Design Aliskiren, a Direct Renin Inhibitor, in Clinical Practice: A New Approach in the Treatment of Hypertension
Current Vascular Pharmacology Meet Our Editorial Board Member
Recent Patents on Anti-Infective Drug Discovery Oxidative and Inflammatory Events in Prion Diseases: Can They Be Therapeutic Targets?
Current Aging Science Theory and Application of Microdialysis in Pharmacokinetic Studies
Current Drug Metabolism Benefits of Chinese Medicine Among Patients with Diabetic Foot: An Expert Review from Clinical Studies
Current Vascular Pharmacology Childhood Infectious Encephalitis: An Overview of Clinical Features, Investigations, Treatment, and Recent Patents
Recent Patents on Inflammation & Allergy Drug Discovery Ion Transporters in Brain Tumors
Current Medicinal Chemistry The Effect of SEX/Gender on Cardiovascular Pharmacology
Current Pharmaceutical Design Antioxidant Nanoparticles for Control of Infectious Disease
Infectious Disorders - Drug Targets Editorial [Hot Topic:Active and Passive Aβ-Immunotherapy: Preclinical and Clinical Studies and Future Directions: Part I (Guest Editors: Michael G. Agadjanyan and David H. Cribbs)]
CNS & Neurological Disorders - Drug Targets