Glia Proinflammatory Cytokine Upregulation as a Therapeutic Target for Neurodegenerative Diseases: Function-Based and Target-Based Discovery Approaches

Linda J. Van Eldik*, Wendy L. Thompson, Hantamalala Ralay Ranaivo, Heather A. Behanna, D. Martin Watterson

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

127 Scopus citations

Abstract

Inflammation is the body's defense mechanism against threats such as bacterial infection, undesirable substances, injury, or illness. The process is complex and involves a variety of specialized cells that mobilize to neutralize and dispose of the injurious material so that the body can heal. In the brain, a similar inflammation process occurs when glia, especially astrocytes and microglia, undergo activation in response to stimuli such as injury, illness, or infection. Like peripheral immune cells, glia in the central nervous system also increase production of inflammatory cytokines and neutralize the threat to the brain. This brain inflammation, or neuroinflammation, is generally beneficial and allows the brain to respond to changes in its environment and dispose of damaged tissue or undesirable substances. Unfortunately, this beneficial process sometimes gets out of balance and the neuroinflammatory process persists, even when the inflammation-provoking stimulus is eliminated. Uncontrolled chronic neuroinflammation is now known to play a key role in the progression of damage in a number of neurodegenerative diseases. Thus, overproduction of proinflammatory cytokines offers a pathophysiology progression mechanism that can be targeted in new therapeutic development for multiple neurodegenerative diseases. We summarize in this chapter the evidence supporting proinflammatory cytokine upregulation as a therapeutic target for neurodegenerative disorders, with a focus on Alzheimer's disease. In addition, we discuss the drug discovery process and two approaches, function-driven and target-based, that show promise for development of neuroinflammation-targeted, disease-modifying therapeutics for multiple neurodegenerative disorders.

Original languageEnglish (US)
Title of host publicationNeuroinflation in Neuronal Death and Repair
EditorsGiacinto Bagetta, Tiziana Corasaniti, Stuart Lipton
Pages277-296
Number of pages20
DOIs
StatePublished - Aug 2 2007

Publication series

NameInternational Review of Neurobiology
Volume82
ISSN (Print)0074-7742

ASJC Scopus subject areas

  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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