Heme Deficiency in Neurons Causes Metabolic Disruptions Similar to Alzheimer's Disease

Bruce Ames
University of California, Berkeley
P30ES01896

Background: Normal aging of the brain and neurodegenerative changes share certain pathological and physiological changes including mitochondrial dysfunction, oxidative stress, and loss of iron homeostasis. Heme synthesis also declines with age. Heme is the major intracellular functional form of iron. It is synthesized in the mitochondria and the decline in synthesis could explain the loss of iron homeostasis in aging. Heme functions in hemoglobin and in a variety of enzymes as well as promoting the growth of nervous tissue.

Advance: To further investigate the role of heme in nerve cell function, these investigators induced heme deficiency in a nerve cell culture system. Heme deficiency was detrimental to normal mitochondrial function, stimulated oxidative stress by activating nitric oxide synthase, altered amyloid proteins, and inhibited zinc and iron homeostasis. The metabolic changes seen during the heme deficiency were similar to those in dysfunction neurons in patients with Alzheimer's disease.

Implication: Common reasons for heme deficiency are iron and vitamin B6 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 Alzheimer's 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, which deserves more research and attention.

Citation: Atamna H, Killilea DW, Killilea AN, Ames BN. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14807-12.