Biomedicine

Surveying the Damage

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Science  28 Oct 2011:
Vol. 334, Issue 6055, pp. 435
DOI: 10.1126/science.334.6055.435-b

Cellular macromolecules such as proteins, lipids, and DNA undergo an increase in oxidative damage with aging, and this damage can have a cascade effect. Oxidation of membrane lipids, for example, produces a reactive product called malondialdehyde (MDA), which can then form adducts with normal cellular proteins, creating new epitopes that are recognized by the immune system, potentially inducing an inflammatory response. A new study presents a plausible model for how these molecular events contribute to age-related macular degeneration (AMD), a form of blindness affecting over 30 million people worldwide. Weismann et al. now show that the immunoregulatory protein complement factor H (CFH) binds MDA with high affinity and blocks MDA-induced inflammation in mice. Interestingly, a variant form of CFH that is associated with an elevated risk of AMD in humans was found to have a lower affinity for MDA. Thus CFH, which is one of the most abundant proteins in plasma, protects mammals from oxidative stress by virtue of its interaction with a specific product of oxidative damage; disruption of this interaction appears to underlie AMD and conceivably other age-related inflammatory diseases.

Nature 478, 76 (2011).

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