Neurodegenerative disorders: the role of peroxynitrite

Inflammatory reaction is thought to be an important contributor to neuronal damage in neurodegenerative disorders such as Alzheimer's disease (AD), Pa rkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclero sis (ALS) and the parkinsonism dementia complex of Guam, Among the toxic ag ents released in brain tissues by activated cells, we focus attention in th is review on peroxynitrite, the product of the reaction between nitric oxid e (NO) and superoxide. Peroxynitrite is a strong oxidizing and nitrating ag ent which can react with all classes of biomolecules. In the CNS it can be generated by microglial cells activated by pro-inflammatory cytokines or be ta-amyloid peptide (beta-A) and by neurons in three different situations: h yperactivity of glutamate neurotransmission: mitochondrial dysfunction and depletion of L-arginine or tetrahydrobiopterin. The first two situations co rrespond to cellular responses to an initial neuronal injury and the peroxy nitrite formed only exacerbates the inflammatory process, whereas in the th ird situation the peroxynitrite generated directly contributes to the initi ation of the neurodegenerative process. (C) 1999 Elsevier Science B.V. All rights reserved.