| First Author | Sanz JM | Year | 2009 |
| Journal | J Immunol | Volume | 182 |
| Issue | 7 | Pages | 4378-85 |
| PubMed ID | 19299738 | Mgi Jnum | J:147118 |
| Mgi Id | MGI:3839466 | Doi | 10.4049/jimmunol.0803612 |
| Citation | Sanz JM, et al. (2009) Activation of microglia by amyloid {beta} requires P2X7 receptor expression. J Immunol 182(7):4378-85 |
| abstractText | Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X(7) subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid beta (Abeta) triggered increases in intracellular Ca(2+) ([Ca(2+)](i)), ATP release, IL-1beta secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X(7)-deleted mice. Likewise, intra-hippocampal injection of Abeta caused a large accumulation of IL-1beta in wild-type but not in P2X(7)(-/-) mice. These observations suggest that Abeta activates a purinergic autocrine/paracrine stimulatory loop of which the P2X(7) receptor is an obligate component. Identification of the P2X(7) receptor as a non-dispensable factor of Abeta-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease. |
