Abstract
Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.
Keywords: alzheimer disease, ferric cycle, heme, iron homeostasis, oxidative stress
Current Neurovascular Research
Title: Ferric Cycle Activity and Alzheimer Disease
Volume: 2 Issue: 3
Author(s): Barney E. Dwyer, Atsushi Takeda, Xiongwei Zhu, George Perry and Mark A. Smith
Affiliation:
Keywords: alzheimer disease, ferric cycle, heme, iron homeostasis, oxidative stress
Abstract: Elevated plasma homocysteine is an independent risk factor for the development of Alzheimer disease, however, the precise mechanisms underlying this are unclear. In this article, we expound on a novel hypothesis depicting the involvement of homocysteine in a vicious circle involving iron dysregulation and oxidative stress designated as the ferric cycle (Dwyer et al., 2004). Moreover, we suspect that the development of a critical heme deficiency in vulnerable neurons is an additional consequence of ferric cycle activity. Oxidative stress and heme deficiency are consistent with many pathological changes found in Alzheimer disease including mitochondrial abnormalities and impaired energy metabolism, cell cycle and cell signaling abnormalities, neuritic pathology, and other features of the disease involving alterations in iron homeostasis such as the abnormal expression of heme oxygenase-1 and iron response protein 2. Based on the ferric cycle concept, we have developed a model of Alzheimer disease development and progression, which offers an explanation for why sporadic Alzheimer disease is different than normal aging and why familial Alzheimer disease and sporadic Alzheimer disease could have different etiologies but a common end-stage.
Export Options
About this article
Cite this article as:
Dwyer E. Barney, Takeda Atsushi, Zhu Xiongwei, Perry George and Smith A. Mark, Ferric Cycle Activity and Alzheimer Disease, Current Neurovascular Research 2005; 2 (3) . https://dx.doi.org/10.2174/1567202054368371
DOI https://dx.doi.org/10.2174/1567202054368371 |
Print ISSN 1567-2026 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5739 |
- 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
Related Articles
-
The Relevance of Supplemental Vitamin D in Malignancies
Anti-Cancer Agents in Medicinal Chemistry Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies
Current Stem Cell Research & Therapy Preclinical and Clinical Studies of Chidamide (CS055/HBI-8000), An Orally Available Subtype-selective HDAC Inhibitor for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry MicroRNA Involvement in the Pathogenesis of Neuroblastoma: Potential for MicroRNA Mediated Therapeutics
Current Pharmaceutical Design Biological Role of Formaldehyde, and Cycles Related to Methylation, Demethylation, and Formaldehyde Production
Mini-Reviews in Medicinal Chemistry Rationale for the Development of Cholinesterase Inhibitors as Anti- Alzheimer Agents
Current Pharmaceutical Design Docosahexaenoic Acid (DHA) Sensitizes Brain Tumor Cells to Etoposide-Induced Apoptosis
Current Molecular Medicine A Direct Interaction Between Mitochondrial Proteins and Amyloid-β Peptide and its Significance for the Progression and Treatment of Alzheimer’s Disease
Current Medicinal Chemistry The Neurotachykinin NK1 Receptor – A Novel Target for Diagnostics and Therapy
Current Molecular Imaging (Discontinued) Protein Trafficking and Alzheimers Disease
Current Alzheimer Research Applications of iTRAQ and TMT Labeling Techniques to the Study of Neurodegenerative Diseases
Current Protein & Peptide Science Molecular Mechanism Aspect of ER Stress in Alzheimer's Disease: Current Approaches and Future Strategies
Current Drug Targets Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer
Current Medicinal Chemistry Glycoconjugates As Vaccines for Cancer Immunotherapy: Clinical Trials and Future Directions
Anti-Cancer Agents in Medicinal Chemistry Antimicrobial Photodynamic Therapy to Kill Gram-negative Bacteria
Recent Patents on Anti-Infective Drug Discovery An Overview of the Chemistry and Pharmacological Potentials of Furanones Skeletons
Current Organic Chemistry Melatonin and Renal Protection: Novel Perspectives from Animal Experiments and Human Studies (Review)
Current Pharmaceutical Design The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents
Letters in Drug Design & Discovery Prostaglandin J2 Family and the Cardiovascular System
Current Vascular Pharmacology Neurotransmitters and Substances of Abuse: Effects on Adult Neurogenesis
Current Neurovascular Research