Evidence for enhanced neuro-inflammatory processes in neurodegenerative diseases and the action of nitrones as potential therapeutics.
A brief review is presented on observations leading to the current notions regarding neuro-inflammatory processes. The greatest focus is on Alzheimer's disease (AD) since this is where the most convincing data has been obtained. A brief summary of observations on the neuroprotective action of alpha-phenyl-tert-butyl-nitrone (PBN) as well as results of research designed to understand its mechanism of action is presented. We hypothesize that the mechanism of action of PBN involves inhibition of signal transduction processes, which are involved in the upregulation of genes mediated by pro-inflammatory cytokines and H2O2 that cause formation of toxic gene products. Results from recent experiments on Kainic acid (KA) mediated brain damage are provided to suggest the validity of the in vivo action of PBN to inhibit neuro-inflammatory processes. The accumulating scientific facts are helping to provide concepts that may become the basis for novel therapeutic approaches to the treatment of several neurodegenerative diseases.
Floyd
R A
RA
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Hensley
K
K
Bing
G
G
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004660:Encephalitis / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000503:physiopathology*; D009589:Nitrogen Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000502:physiology
D009589:Nitrogen Oxides; C015388:nitrones