Neuroinflammation: a potential therapeutic target.
The increased appreciation of the importance of glial cell-propagated inflammation (termed 'neuroinflammation') in the progression of pathophysiology for diverse neurodegenerative diseases, has heightened interest in the rapid discovery of neuroinflammation-targeted therapeutics. Efforts include searches among existing drugs approved for other uses, as well as development of novel synthetic compounds that selectively downregulate neuroinflammatory responses. The use of existing drugs to target neuroinflammation has largely met with failure due to lack of efficacy or untoward side effects. However, the de novo development of new classes of therapeutics based on targeting selective aspects of glia activation pathways and glia-mediated pathophysiologies, versus targeting pathways of quantitative importance in non-CNS inflammatory responses, is yielding promising results in preclinical animal models. The authors briefly review selected clinical and preclinical data that reflect the prevailing approaches targeting neuroinflammation as a pathophysiological process contributing to onset or progression of neurodegenerative diseases. The authors conclude with opinions based on recent experimental proofs of concept using preclinical animal models of pathophysiology. The focus is on Alzheimer's disease, but the concepts are transferrable to other neurodegenerative disorders with an inflammatory component.
Craft
Jeffrey M
JM
Center for Drug Discovery and Chemical Biology, Northwestern University, Feinberg School of Medicine, 303 E. Chicago Avenue, Mail Code W-896, Chicago, IL 60611-3008,USA.
Watterson
D Martin
DM
Van Eldik
Linda J
LJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use*; D002493:Central Nervous System Diseases / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal