Microglia as a pharmacological target in infectious and inflammatory diseases of the brain.
Following an eclipse of scientific inquiry regarding the biology of microglia that lasted 50 years, recognition toward the end of the 20th century of their neuropathogenic role in HIV-associated dementia and in neuroinflammatory/neurodegenerative diseases fueled a renaissance of interest in these resident macrophages of the brain parenchyma. Results of a large number of in vitro studies, using isolated microglial cells or glial/neuronal cell cultures, and parallel findings emerging from animal models and clinical studies have demonstrated that activated microglia produce a myriad of inflammatory mediators that both serve important defense functions against invading neurotropic pathogens and have been implicated in brain damage in infectious as well as neuroinflammatory/neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review provides a brief background regarding the physiological and pathophysiological roles of microglia and highlights current pharmacological approaches that target activated microglia with the goal of ameliorating infectious and neuroinflammatory/neurodegenerative diseases of the brain. Although this aspect of the field of neuroimmunopharmacology is in its infancy, it holds great promise for developing new treatments and prevention of diseases that are, in many cases, epidemic throughout the world.
Center for Infectious Diseases and Microbiology, Translational Research and the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
R Bryan
RB
Rock
Phillip K
PK
Peterson
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D001927:Brain Diseases / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D003141:Communicable Diseases / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000893:Anti-Inflammatory Agents