| First Author | Shie FS | Year | 2005 |
| Journal | Am J Pathol | Volume | 166 |
| Issue | 4 | Pages | 1163-72 |
| PubMed ID | 15793296 | Mgi Jnum | J:97062 |
| Mgi Id | MGI:3574218 | Doi | 10.1016/s0002-9440(10)62336-x |
| Citation | Shie FS, et al. (2005) Microglia Lacking E Prostanoid Receptor Subtype 2 Have Enhanced A{beta} Phagocytosis yet Lack A{beta}-Activated Neurotoxicity. Am J Pathol 166(4):1163-72 |
| abstractText | Experimental therapies for Alzheimer's disease (AD) are focused on enhanced clearance of neurotoxic Abeta peptides from brain. Microglia can be neuroprotective by phagocytosing Abeta; however, this comes at the cost of activated innate immunity that causes paracrine damage to neurons. Here, we show that ablation of E prostanoid receptor subtype 2 (EP2) significantly increased microglial-mediated clearance of Abeta peptides from AD brain sections and enhanced microglial Abeta phagocytosis in cell culture. The enhanced phagocytosis was PKC-dependent and was associated with elevated microglial secretion of the chemoattractant chemokines, macrophage inflammatory protein-1alpha and macrophage chemoattractant protein-1. This suggested that microglial activation is negatively regulated by EP2 signaling through suppression of prophagocytic cytokine secretion. However, despite this enhancement of Abeta phagocytosis, lack of EP2 completely suppressed Abeta-activated microglia-mediated paracrine neurotoxicity. These data demonstrate that blockade of microglial EP2 is a highly desirable mechanism for AD therapy that can maximize neuroprotective actions while minimizing bystander damage to neurons. |
