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Published on: April 13, 2017
Microglia as a pharmacological target in infectious and inflammatory diseases of the brain
R Bryan Rock1, Phillip K Peterson
1Center for Infectious Diseases and Microbiology, Translational Research and the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
Abstract:
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.
Insights
Microglia, the brain's immune cells, play a dual role in defense and disease. Targeting activated microglia offers promising new treatments for neuroinflammatory and neurodegenerative diseases.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Neurodegenerative Diseases
Background:
- Microglia, resident brain macrophages, were understudied for 50 years.
- Renewed interest emerged due to their role in HIV-associated dementia and neuroinflammation.
- Activated microglia produce inflammatory mediators with both protective and damaging effects.
Purpose of the Study:
- To review the physiological and pathophysiological roles of microglia.
- To highlight current pharmacological strategies targeting activated microglia.
- To explore the therapeutic potential of targeting microglia in brain diseases.
Main Methods:
- In vitro studies with isolated microglia and cell cultures.
- In vivo studies using animal models.
- Analysis of clinical data and human studies.
Main Results:
- Activated microglia contribute to brain damage in various diseases.
- Microglia are implicated in multiple sclerosis, Alzheimer's, Parkinson's, and ALS.
- Inflammatory mediators produced by microglia have complex roles.
Conclusions:
- Targeting activated microglia is a developing area in neuroimmunopharmacology.
- This approach holds significant promise for treating widespread brain diseases.
- Further research is needed to develop effective treatments and prevention strategies.
