PMID: 9185121May 1, 1997Paper

The possible role of peroxynitrite in Alzheimer's disease: a simple hypothesis that could be tested more thoroughly

Medical Hypotheses
K Van Dyke

Abstract

Alzheimer's disease is characterized by the development of a degenerative condition in the elderly, associated with dementia. Upon pathological examination, cerebral amyloid plaques are found which contain denatured protein or peptide material. The process of denaturation of protein requires the presence of excessive heat, organic solvents, or oxidizing acids (OA). It seems that only OA could produce these effects since the other two are not present in the disease. Macrophages can produce the anion of an oxidizing acid known as peroxynitrite (OONO). This material is formed from two free radical gases, namely superoxide anion [.O2]- and nitric oxide (.N = O). Although (OONO)- is very reactive (1000 times more oxidizing than hydrogen peroxide), its half life in solution is only 1 to 2 seconds. Therefore, when it oxidizes a substance (such as protein) peroxynitrite disappears. The brain contains cells called microglia which are produced from monocytes in the same way as other types of macrophages from the lung and liver etc. The macrophages from the lung (alveolar) and liver (Kupfer cells) produce large amounts of peroxynitrite when activated by particles (silica) or infectious agents (lipopolysaccharide or interferon). Microglia ...Continue Reading

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