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.
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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 |
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