Ferric cycle activity and Alzheimer disease

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

研究成果: Review article査読

12 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)261-267
ページ数7
ジャーナルCurrent Neurovascular Research
2
3
DOI
出版ステータスPublished - 2005 7 1

ASJC Scopus subject areas

  • 神経学
  • 発達神経科学
  • 細胞および分子神経科学

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