Authors: Dwyer, Barney E.; Takeda, Atsushi; Zhu, Xiongwei; Perry, George; Smith, Mark A.

Source: Current Neurovascular Research, Volume 2, Number 3, July 2005 , pp. 261-267(7)

Publisher: Bentham Science Publishers

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

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1567202054368371

Affiliations: 1: Institute of Pathology; Case Western Reserve University; 2085 Adelbert Road; Cleveland, Ohio 44106 USA.

Publication date: 2005-07-01

More about this publication?

• Current Neurovascular Research (CNR) provides a cross platform for the publication of scientifically rigorous research that addresses disease mechanisms of both neuronal and vascular origins in neuroscience. The journal serves as an international forum for the publication of novel and pioneering original work as well as timely neuroscience research reviews in the disciplines of cell developmental disorders, plasticity, and degeneration that bridge the gap between basic science research and clinical discovery. CNR emphasizes the elucidation of disease mechanisms, both cellular and molecular, which can impact the development of unique therapeutic strategies for neuronal and vascular disorders.

Related content

• In this: publication
• By this: publisher
• In this Subject: Neurology & Psychiatry
• By this author: Dwyer, Barney E. ;  Takeda, Atsushi ;  Zhu, Xiongwei ;  Perry, George ;  Smith, Mark A.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers