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Aluminum Induced Immunoexcitotoxicity in Neurodevelopmental and Neurodegenerative Disorders *

A great deal has been learned about the neurotoxicity of aluminum over the past two decades in terms of its ability to disrupt cellular function. Newer evidence suggests that a more central pathophysiological mechanism may be responsible for much of the toxicity of aluminum and aluminofluoride compounds on the brain. This mechanism involves activation of the brain’s innate immune system, primarily the microglia, with a release of neurotoxic concentrations of excitotoxins and pro-inflammatory cytokines, chemokines and immune mediators. A large number of studies suggest that excitotoxicity plays a significant role in the neurotoxic action of a number of metals, including aluminum. Recently, researchers have found that while most of the chronic neurodegenerative effects of these metals are secondary to prolonged inflammation, it is the enhancement of excitotoxicity by the immune mediators that is responsible for most of the metal’s toxicity. This enhancement occurs via a crosstalk between cytokine receptors and glutamate receptors. The author coined the name immunoexcitotoxicity to describe this process. This paper reviews the evidence linking immunoexcitotoxicity to aluminum’s neurotoxic effects.

URL: http://www.ingentaconnect.com/content/ben/cic/2012/00000002/00000001/art00006

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Published on 11-13-2014