| First Author | Kim HJ | Year | 2012 |
| Journal | J Neurochem | Volume | 121 |
| Issue | 2 | Pages | 228-38 |
| PubMed ID | 22353164 | Mgi Jnum | J:184286 |
| Mgi Id | MGI:5320682 | Doi | 10.1111/j.1471-4159.2012.07700.x |
| Citation | Kim HJ, et al. (2012) Nucleotides released from Abeta(1)(-)(4)(2) -treated microglial cells increase cell migration and Abeta(1)(-)(4)(2) uptake through P2Y(2) receptor activation. J Neurochem 121(2):228-38 |
| abstractText | Amyloid beta-protein (Abeta) deposits in brains of Alzheimer's disease patients generate proinflammatory cytokines and chemokines that recruit microglial cells to phagocytose Abeta. Nucleotides released from apoptotic cells activate P2Y(2) receptors (P2Y(2) Rs) in macrophages to promote clearance of dead cells. In this study, we investigated the role of P2Y(2) Rs in the phagocytosis and clearance of Abeta. Treatment of mouse primary microglial cells with fibrillar (fAbeta(1-42) ) and oligomeric (oAbeta(1-42) ) Abeta(1-42) aggregation solutions caused a rapid release of ATP (maximum after 10 min). Furthermore, fAbeta(1-42) and oAbeta(1-42) treatment for 24 h caused an increase in P2Y(2) R gene expression. Treatment with fAbeta(1-42) and oAbeta(1-42) aggregation solutions increased the motility of neighboring microglial cells, a response inhibited by pre-treatment with apyrase, an enzyme that hydrolyzes nucleotides. The P2Y(2) R agonists ATP and UTP caused significant uptake of Abeta(1-42) by microglial cells within 30 min, which reached a maximum within 1 h, but did not increase Abeta(1-42) uptake by primary microglial cells isolated from P2Y(2) R(-/-) mice. Inhibitors of alpha(v) integrins, Src and Rac decreased UTP-induced Abeta(1-42) uptake, suggesting that these previously identified components of the P2Y(2) R signaling pathway play a role in Abeta phagocytosis by microglial cells. Finally, we found that UTP treatment enhances Abeta(1-42) degradation by microglial cells, but not in cells isolated from P2Y(2) R(-/-) mice. Taken together, our findings suggest that P2Y(2) Rs can activate microglial cells to enhance Abeta clearance and highlight the P2Y(2) R as a therapeutic target in Alzheimer's disease. |
