Neuroinflammatory processes are important in neurodegenerative diseases: An hypothesis to explain the increased formation of reactive oxygen and nitrogen species as major factors involved in neurodegenerative disease development

The hypothesis, as stated in the title, has arisen from the failure of simp ler notions to explain a series of otherwise difficult to understand observ ations and the mounting evidence, in a broader sense, that inflammatory pro cesses in the CNS are important etiologically in neurodegenerative diseases . Novel aspects include the primacy of inflammatory processes, within the C NS, which leads to increased formation of "proinflammatory" cytokines that lead to increased formation of reactive oxygen species (ROS) and mediation of the upregulation of genes that produce toxic products such as reactive n itrogen species (RNS). Here I utilize important background reports and synt hesize ideas to help account for the noted increases in ROS and RNS and the ir biological reaction products in neurodegenerative diseases. The uniquene ss of the CNS inflammatory processes include minimal damping of amplificati on processes, such as proinflammatory cytokine-mediated cascades, combined with unique genetic defects, that act in combination with other risk factor s to repeatedly "spark" the inflammatory cascades to account for some of th e major differences in neurodegenerative diseases. This hypothesis can be e xperimentally examined by development of definitive methods to quantitate u nique products that are formed by processes predicted to occur under neurod egenerative conditions. (C) 1999 Elsevier Science Inc.