Abstract
Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer ’ s disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal development and polarity, as well as in axon growth and guidance. In this mini-review, we examine what is known about CRMP2 function, how that is controlled by phosphorylation, what alterations in molecular mechanisms could lead to the abnormally high CRMP2 phosphorylation in AD, and whether this is likely to be specific to AD or occur in other forms of neurodegeneration. This will include discussion of the evidence for increased GSK3 or Cdk5 activity, for decreased phosphatase activity, or the upregulation of other CRMP2 protein kinases in AD. Importantly, we will compare the processes that may contribute to increased CRMP2 phosphorylation with those known to increase tau hyperphosphorylation in AD, and whether these are likely to be part of disease development or a useful early marker for AD.
Current Alzheimer Research
Title: Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?
Volume: 6 Issue: 3
Author(s): M. P.M. Soutar, P. Thornhill, A. R. Cole and C. Sutherland
Affiliation:
Abstract: Collapsin response mediator protein-2 (CRMP2) was recently identified as a physiological substrate for GSK3 and Cdk5, two protein kinases suggested to exhibit greater activity in Alzheimer ’ s disease (AD). Indeed, phosphorylation of CRMP2, at the residues targeted by GSK3 and Cdk5, is relatively high in cortex isolated from human AD brain, as well as in the brains of animal models of AD, while phospho-CRMP2 is found in neurofibrillary tangles. In mouse models of AD, increased phosphorylation occurs prior to pathology. Although CRMP2 has no known enzymatic activity, a great deal of information is appearing on its importance in neuronal development and polarity, as well as in axon growth and guidance. In this mini-review, we examine what is known about CRMP2 function, how that is controlled by phosphorylation, what alterations in molecular mechanisms could lead to the abnormally high CRMP2 phosphorylation in AD, and whether this is likely to be specific to AD or occur in other forms of neurodegeneration. This will include discussion of the evidence for increased GSK3 or Cdk5 activity, for decreased phosphatase activity, or the upregulation of other CRMP2 protein kinases in AD. Importantly, we will compare the processes that may contribute to increased CRMP2 phosphorylation with those known to increase tau hyperphosphorylation in AD, and whether these are likely to be part of disease development or a useful early marker for AD.
Export Options
About this article
Cite this article as:
Soutar P.M. M., Thornhill P., Cole R. A. and Sutherland C., Increased CRMP2 Phosphorylation is Observed in Alzheimers Disease; Does this Tell us Anything About Disease Development?, Current Alzheimer Research 2009; 6 (3) . https://dx.doi.org/10.2174/156720509788486572
DOI https://dx.doi.org/10.2174/156720509788486572 |
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
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
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...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
-
Antioxidant Effects of Chalcones during the Inflammatory Response: An Overall Review
Current Medicinal Chemistry Akt Pathway Inhibitors
Current Topics in Medicinal Chemistry Modulation of Mitochondrial and Epigenetic Targets by Polyphenols-rich Extract from Araucaria angustifolia in Larynx Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Iron Oxide Nanoparticle Platform for Biomedical Applications
Current Medicinal Chemistry Molecular Mechanisms of Anti-cancer Action of Garlic Compounds in Neuroblastoma
Anti-Cancer Agents in Medicinal Chemistry Allosteric Modulation of Nicotinic Acetylcholine Receptors: The Concept and Therapeutic Trends
Current Pharmaceutical Design Recent Advances in Oncogenic Roles of the TRPM7 Chanzyme
Current Medicinal Chemistry The Role of the Osteoimmune Axis in the Inflammation of the Inner Auditory Ear and with Regard to the Putative Anticarcinogenetic Principle: Part 2
Inflammation & Allergy - Drug Targets (Discontinued) Advances in Hydrogels Applied to Degenerative Diseases
Current Pharmaceutical Design Addictions and Stress: Clues for Cocaine Pharmacotherapies
Current Pharmaceutical Design The Novel Multi-Target Iron Chelator, M30 Modulates HIF-1α-Related Glycolytic Genes and Insulin Signaling Pathway in the Frontal Cortex of APP/PS1 Alzheimer’s Disease Mice
Current Alzheimer Research Nephrotoxicity of Bisphenol A (BPA) -An Updated Review
Current Molecular Pharmacology Perturbation of HSP Network in MCF-7 Breast Cancer Cell Line Triggers Inducible HSP70 Expression and Leads to Tumor Suppression
Anti-Cancer Agents in Medicinal Chemistry C-Myc Signaling Pathway in Treatment and Prevention of Brain Tumors
Current Cancer Drug Targets Design, Synthesis, and Anti-Neuroinflammatory Activity of Amide- Containing Dithiolethiones
Medicinal Chemistry Therapeutic Potential of Multifunctional Tacrine Analogues
Current Neuropharmacology Interleukin-6: A Critical Cytokine in Cancer Multidrug Resistance
Current Pharmaceutical Design Neuroblastoma and Stem Cell Therapy: An Updated Review
CNS & Neurological Disorders - Drug Targets Carbohydrate Mimotopes in the Rational Design of Cancer Vaccines
Current Topics in Medicinal Chemistry Radiobromine-Labelled Tracers for Positron Emission Tomography: Possibilities and Pitfalls
Current Radiopharmaceuticals