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 simpler notions to explain a series of otherwise difficult to understand observations and the mounting evidence, in a broader sense, that inflammatory processes in the CNS are important etiologically in neurodegenerative diseases. Novel aspects include the primacy of inflammatory processes, within the CNS, 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 nitrogen species (RNS). Here I utilize important background reports and synthesize ideas to help account for the noted increases in ROS and RNS and their biological reaction products in neurodegenerative diseases. The uniqueness of the CNS inflammatory processes include minimal damping of amplification processes, such as proinflammatory cytokine-mediated cascades, combined with unique genetic defects, that act in combination with other risk factors to repeatedly "spark" the inflammatory cascades to account for some of the major differences in neurodegenerative diseases. This hypothesis can be experimentally examined by development of definitive methods to quantitate unique products that are formed by processes predicted to occur under neurodegenerative conditions. (C) 1999 Elsevier Science Inc.