Abstract
The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients. It has recently become clear that AGEs also influence physiological aging and neurodegenerative diseases such as Alzheimers disease (AD) and amyotrophic lateral sclerosis (ALS). Recently we have provided direct immunochemical evidence for the existence of six distinct AGE structures within the AGE-modified proteins and peptides that circulate in the serum of diabetic patients on hemodialysis (DM-HD). We showed a direct toxic effect of the synthetic AGE-2 (glyceraldehyde-derived AGEs) on cortical neuronal cells and provided evidence for a toxic effect of AGE-2 present in DM-HD serum. These results indicate that of the various types of AGE structures that can form in vivo, the AGE-2 structure is likely to play an important role in the pathophysiological processes associated with AGE formation. In AD brains, AGE-2 epitope was mainly present in the cytosol of neurons in the hippocampus and para-hipocampal gyrus. Protein cross-linking by AGE structures results in the formation of protease-resistant aggregates. Such protein aggregates may interfere with both axonal transport and intracellular protein traffic in neuron. In this review, we provide an outline of AGEs formation in vivo and propose that the novel structural epitope AGE-2 is an important toxic moiety for neuronal cells in AD.
Keywords: advanced glycation end-products (AGEs), glyceraldehyde-derived AGEs, AGE-2 structure, Alzheimers disease (AD), diabetes mellitus (DM), neurotoxicity, apoptosis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Current Alzheimer Research
Title: Involvement of Advanced Glycation End-products (AGEs) in Alzheimers Disease
Volume: 1 Issue: 1
Author(s): Masayoshi Takeuchi, Seiji Kikuchi, Nobuyuki Sasaki, Takako Suzuki, Takayuki Watai, Mina Iwaki, Richard Bucala and Sho-ichi Yamagishi
Affiliation:
Keywords: advanced glycation end-products (AGEs), glyceraldehyde-derived AGEs, AGE-2 structure, Alzheimers disease (AD), diabetes mellitus (DM), neurotoxicity, apoptosis, glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
Abstract: The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients. It has recently become clear that AGEs also influence physiological aging and neurodegenerative diseases such as Alzheimers disease (AD) and amyotrophic lateral sclerosis (ALS). Recently we have provided direct immunochemical evidence for the existence of six distinct AGE structures within the AGE-modified proteins and peptides that circulate in the serum of diabetic patients on hemodialysis (DM-HD). We showed a direct toxic effect of the synthetic AGE-2 (glyceraldehyde-derived AGEs) on cortical neuronal cells and provided evidence for a toxic effect of AGE-2 present in DM-HD serum. These results indicate that of the various types of AGE structures that can form in vivo, the AGE-2 structure is likely to play an important role in the pathophysiological processes associated with AGE formation. In AD brains, AGE-2 epitope was mainly present in the cytosol of neurons in the hippocampus and para-hipocampal gyrus. Protein cross-linking by AGE structures results in the formation of protease-resistant aggregates. Such protein aggregates may interfere with both axonal transport and intracellular protein traffic in neuron. In this review, we provide an outline of AGEs formation in vivo and propose that the novel structural epitope AGE-2 is an important toxic moiety for neuronal cells in AD.
Export Options
About this article
Cite this article as:
Takeuchi Masayoshi, Kikuchi Seiji, Sasaki Nobuyuki, Suzuki Takako, Watai Takayuki, Iwaki Mina, Bucala Richard and Yamagishi Sho-ichi, Involvement of Advanced Glycation End-products (AGEs) in Alzheimers Disease, Current Alzheimer Research 2004; 1 (1) . https://dx.doi.org/10.2174/1567205043480582
DOI https://dx.doi.org/10.2174/1567205043480582 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
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
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
-
Metal Transport and Homeostasis within the Human Body: Toxicity Associated with Transport Abnormalities
Current Medicinal Chemistry Gastric Inhibitory Polypeptide and its Receptor are Expressed in the Central Nervous System and Support Neuronal Survival
Central Nervous System Agents in Medicinal Chemistry Molecular Dynamics and Regulation of Butyrylcholinesterase Cholinergic Activity by RNA Binding Proteins
CNS & Neurological Disorders - Drug Targets Relevance of Follow-Up in Patients with Core Clinical Criteria for Alzheimer Disease and Normal CSF Biomarkers
Current Alzheimer Research Human Tooth Germ Stem Cells Preserve Neuro-Protective Effects after Long-Term Cryo-Preservation
Current Neurovascular Research Neurological Aspects of Medical Use of Cannabidiol
CNS & Neurological Disorders - Drug Targets Oxidative Stress Protection by Novel Telomerase Activators in Mesenchymal Stem Cells Derived from Healthy and Diseased Individuals
Current Molecular Medicine Glutamate Receptors in Human Caudate Nucleus in Normal Aging and Alzheimer’s Disease
Current Alzheimer Research Current Therapeutic Molecules and Targets in Neurodegenerative Diseases Based on in silico Drug Design
Current Neuropharmacology Prediction of Disease-Related Genes Based on Hybrid Features
Current Proteomics Neurodegeneration and Neuroprotection in Multiple Sclerosis
Current Pharmaceutical Design Looking for New Antifungal Drugs from Flavonoids: Impact of the Genetic Diversity of Candida albicans on the in-vitro Response
Current Medicinal Chemistry Tracking Stem Cells for Cellular Therapy in Stroke
Current Pharmaceutical Design Towards Environmental Construct Validity in Animal Models of CNS Disorders: Optimizing Translation of Preclinical Studies
CNS & Neurological Disorders - Drug Targets Challenges in Neuronal Apoptosis
Current Alzheimer Research Adeno-Associated Virus (AAV) Vectors in the CNS
Current Gene Therapy Subject Index To Volume 1
Recent Patents on CNS Drug Discovery (Discontinued) Interaction of Dehydrogenase Enzymes with Nanoparticles in Industrial and Medical Applications, and the Associated Challenges: A Mini-review
Mini-Reviews in Medicinal Chemistry Mini-Review: Nucleus-Targeted Ribonucleases As Antitumor Drugs
Current Medicinal Chemistry A Neurotrophic Rationale for the Therapy of Neurodegenerative Disorders
Current Alzheimer Research