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
-
Evaluation of Anticancer, Antibacterial and Antioxidant Properties of a Medicinally Treasured Fern Tectaria coadunata with its Phytoconstituents Analysis by HR-LCMS
Anti-Cancer Agents in Medicinal Chemistry Perinatal Management of Fetal Tumors
Current Pediatric Reviews The Other Side of Opioid Receptor Signalling: Regulation by Protein-Protein Interaction
Current Drug Targets Anti-cancer and Other Bioactivities of Korean Angelica gigas Nakai (AGN) and Its Major Pyranocoumarin Compounds
Anti-Cancer Agents in Medicinal Chemistry 5-ht6 Receptors
Current Drug Targets - CNS & Neurological Disorders Identification of Fish Cell Lines Using 2-D Electrophoresis Based Protein Expression Signatures
Current Proteomics Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment
Mini-Reviews in Medicinal Chemistry Mechanisms Underlying Chemopreventive Effects of Flavonoids via Multiple Signaling Nodes within Nrf2-ARE and AhR-XRE Gene Regulatory Networks
Current Chemical Biology Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Chlorogenic Acid and Mental Diseases: From Chemistry to Medicine
Current Neuropharmacology Gold(III) Complexes in the Oncological Preclinical Arena: From Aminoderivatives to Peptidomimetics
Current Topics in Medicinal Chemistry Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020)
Current Medicinal Chemistry Melittin: A Natural Peptide with Expanded Therapeutic Applications
The Natural Products Journal Polyphenols: Well Beyond The Antioxidant Capacity: Gallic Acid and Related Compounds as Neuroprotective Agents: You are What You Eat!
Current Pharmaceutical Biotechnology Heme Oxygenase-1 in Tumor Biology and Therapy
Current Drug Targets Removing Protein Aggregates: The Role of Proteolysis in Neurodegeneration
Current Medicinal Chemistry Molecular and Cellular Mechanisms for Alzheimers Disease:Understanding APP Metabolism
Current Molecular Medicine Current Drug Targets for Modulating Alzheimer's Amyloid Precursor Protein: Role of Specific Micro-RNA Species
Current Medicinal Chemistry Neuroprotection with Natural Antioxidants and Nutraceuticals in the Context of Brain Cell Degeneration: The Epigenetic Connection
Current Topics in Medicinal Chemistry Identification of Functional Peptides from Natural and Synthetic Products on Their Anticancer Activities by Tumor Targeting
Current Medicinal Chemistry