Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease

Fonseca, Maria I., Ager, Rahasson R., Chu, Shu-Hui, Yazan, Ozkan, Sanderson, Sam D., LaFerla, Frank M., Taylor, Stephen M., Woodruff, Trent M. and Tenner, Andrea J. (2009) Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. Journal of Immunology, 183 2: 1375-1383. doi:10.4049/jimmunol.0901005


Author Fonseca, Maria I.
Ager, Rahasson R.
Chu, Shu-Hui
Yazan, Ozkan
Sanderson, Sam D.
LaFerla, Frank M.
Taylor, Stephen M.
Woodruff, Trent M.
Tenner, Andrea J.
Title Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
1550-6606
Publication date 2009-07-15
Sub-type Article (original research)
DOI 10.4049/jimmunol.0901005
Volume 183
Issue 2
Start page 1375
End page 1383
Total pages 9
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Collection year 2010
Language eng
Subject 06 Biological Sciences
11 Medical and Health Sciences
Formatted abstract
Alzheimer’s disease (AD) is an age-related dementia, characterized by amyloid plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss in the brain. Components of the complement system, known to produce a local inflammatory reaction, are associated with the plaques and tangles in AD brain, and thus a role for complement-mediated inflammation in the acceleration or progression of disease has been proposed. A complement activation product, C5a, is known to recruit and activate microglia and astrocytes in vitro by activation of a G protein-coupled cell-surface C5aR. Here, oral delivery of a cyclic hexapeptide C5a receptor antagonist (PMX205) for 2–3 mo resulted in substantial reduction of pathological markers such as fibrillar amyloid deposits (49–62%) and activated glia (42–68%) in two mouse models of AD. The reduction in pathology was correlated with improvements in a passive avoidance behavioral task in Tg2576 mice. In 3xTg mice, PMX205 also significantly reduced hyperphosphorylated tau (69%). These data provide the first evidence that inhibition of a proinflammatory receptor-mediated function of the complement cascade (i.e., C5aR) can interfere with neuroinflammation and neurodegeneration in AD rodent models, suggesting a novel therapeutic target for reducing pathology and improving cognitive function in human AD patients.
Keyword Complement factor 5A
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 83 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 91 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Thu, 03 Sep 2009, 07:50:25 EST by Mr Andrew Martlew on behalf of Library Corporate Services