Woodling, N.S. and Andreasson, K.I. (2016) Untangling the web: toxic and protective effects of neuroinflammation and PGE2 signaling in Alzheimer's disease. ACS Chemical Neuroscience, 7(4), pp. 454-463. (doi: 10.1021/acschemneuro.6b00016) (PMID:26979823) (PMCID:PMC5239037)
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Abstract
The neuroinflammatory response has received increasing attention as a key factor in the pathogenesis of Alzheimer’s disease (AD). Microglia, the innate immune cells and resident phagocytes of the brain, respond to accumulating Aβ peptides by generating a nonresolving inflammatory response. While this response can clear Aβ peptides from the nervous system in some settings, its failure to do so in AD accelerates synaptic injury, neuronal loss, and cognitive decline. The complex molecular components of this response are beginning to be unraveled, with identification of both damaging and protective roles for individual components of the neuroinflammatory response. Even within one molecular pathway, contrasting effects are often present. As one example, recent studies of the inflammatory cyclooxygenase–prostaglandin pathway have revealed both beneficial and detrimental effects dependent on the disease context, cell type, and downstream signaling pathway. Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenases, are associated with reduced AD risk when taken by cognitively normal populations, but additional clinical and mouse model studies have added complexities and caveats to this finding. Downstream of cyclooxygenase activity, prostaglandin E2 signaling exerts both damaging pro-inflammatory and protective anti-inflammatory effects through actions of specific E-prostanoid G-protein coupled receptors on specific cell types. These complexities underscore the need for careful study of individual components of the neuroinflammatory response to better understand their contribution to AD pathogenesis and progression.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Woodling, Dr Nathan |
| Authors: | Woodling, N.S., and Andreasson, K.I. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | ACS Chemical Neuroscience |
| Publisher: | American Chemical Society |
| ISSN: | 1948-7193 |
| Published Online: | 04 April 2016 |
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