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Heme deficiency effects offer clue to Alzheimer disease. (Aging).

Atamna H, Killilea DW, Killilea AN, Ames BN. 2002. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc Nad Acad Sci U S A. 99(23):14807-14812.

Normal aging of the brain and the neurodegeneration caused by Alzheimer disease (AD) share several pathological changes, including mitochondrial dysfunction, oxidative stress, and loss of iron homeostasis. Synthesis of heme--the major intracellular functional form of iron--declines with age. Heme functions in hemoglobin and in a variety of enzymes and promotes the growth of nerve tissue. NIEHS grantee Bruce Ames and colleagues at the Children's Hospital Oakland Research Institute in Oakland, California, investigated the effect of a decline in heme on nerve cell function.

The investigators induced heme deficiency in a nerve cell culture system. The results of the study showed that heme deficiency in brain cells deterred normal mitochondrial function, stimulated oxidative stress and damage by activating synthesis of nitric oxide, altered amyloid proteins, and inhibited zinc and iron homeostasis. The metabolic changes that resulted from the heme deficiency were similar to those seen in dysfunctional neurons in patients with AD. In particular, in this model of heme deficiency, iron was the last parameter to change.

These findings are consistent, the authors say, with the hypothesis that an alteration in heme metabolism is the driving force for iron to accumulate in the cell. A marked increase in zinc and iron is associated with extracellular plaques found in AD patients, suggesting a disruption of metal homeostasis.

Common reasons for heme deficiency are iron and vitamin [B.sub.6] deficiencies, aging, and exposure to toxic metals such as aluminum, in addition, degradation of heme by heme oxygenase, which increases with age and in the brains of AD patients, may be a factor in changes in the metabolism of iron and heme with age. Therefore, heme deficiency may be an important and preventable part of the neurodegenerative process.
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Author:Phelps, Jerry
Publication:Environmental Health Perspectives
Date:Mar 1, 2003
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