Affordable Access

deepdyve-link
Publisher Website

Therapeutic implications of the prostaglandin pathway in Alzheimer's disease

Authors
  • Cudaback, Eiron
  • Jorstad, Nikolas L.
  • Yang, Yue
  • Montine, Thomas J.
  • Keene, C. Dirk1
  • 1 University of Washington Harborview Medical Center, Department of Pathology
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Dec 18, 2013
Identifiers
DOI: 10.1016/j.bcp.2013.12.014
Source
Elsevier
Keywords
License
Unknown

Abstract

An important pathologic hallmark of Alzheimer's disease (AD) is neuroinflammation, a process characterized in AD by disproportionate activation of cells (microglia and astrocytes, primarily) of the non-specific innate immune system within the CNS. While inflammation itself is not intrinsically detrimental, a delicate balance of pro- and anti-inflammatory signals must be maintained to ensure that long-term exaggerated responses do not damage the brain over time. Non-steroidal anti-inflammatory drugs (NSAIDs) represent a broad class of powerful therapeutics that temper inflammation by inhibiting cyclooxygenase-mediated signaling pathways including prostaglandins, which are the principal mediators of CNS neuroinflammation. While historically used to treat discrete or systemic inflammatory conditions, epidemiologic evidence suggests that protracted NSAID use may delay AD onset, as well as decrease disease severity and rate of progression. Unfortunately, clinical trials with NSAIDs have thus far yielded disappointing results, including premature discontinuation of a large-scale prevention trial due to unexpected cardiovascular side effects. Here we review the literature and make the argument that more targeted exploitation of downstream prostaglandin signaling pathways may offer significant therapeutic benefits for AD while minimizing adverse side effects. Directed strategies such as these may ultimately help to delay the deleterious consequences of brain aging and might someday lead to new therapies for AD and other chronic neurodegenerative diseases.

Report this publication

Statistics

Seen <100 times