Monif et al. have published an excellent paper. It provides independent confirmation of our earlier finding that the P2X7 receptor, far from being a mere "death receptor," is on the contrary a growth-promoting receptor (see Baricordi et al., 1999). We strengthened this finding in subsequent papers (Adinolfi et al., 2002; Adinolfi et al., 2005; Raffaghello et al., 2006). We also showed, in collaboration with Claudia Verderio and Maria Pia Abbracchio, that the P2X7 receptor had a crucial role in sustaining growth of microglia and discussed implications for neurodegenerative diseases (Bianco et al., 2006). In two recent papers we have further analyzed the molecular basis of the trophic effect of P2X7 (Adinolfi et al., 2009), and discussed the implications in cancer (Di Virgilio et al., 2009).

References:
Baricordi OR, Melchiorri L, Adinolfi E, Falzoni S, Chiozzi P, Buell G, Di Virgilio F. (1999) Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J Biol Chem. 274:33206-8. Abstract

Adinolfi E, Melchiorri L, Falzoni S, Chiozzi P, Morelli A, Tieghi A, Cuneo A, Castoldi G, Di Virgilio F, Baricordi OR. (2002) P2X7 receptor expression in evolutive and indolent forms of chronic lymphocytic leukemia. Blood 99: 706-708. Abstract

Adinolfi E, Callegari MG, Ferrari D, Bolognesi C, Minelli M, Wieckowski MR, Pinton P, Rizzuto R, Di Virgilio F. (2005) Basal activation of the P2X7 receptor elevates mitochondrial calcium and potential, increases cellular ATP levels, and promotes serum-independent growth. Mol Biol Cell 16: 3260-3272. Abstract

Raffaghello L, Chiozzi P, Falzoni S, Di Virgilio F, and Pistoia V. (2006) The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. Cancer Res 66:907-914. Abstract

Bianco F, Ceruti S, Colombo A, Fumagalli M, Ferrari D, Pizzirani C, Matteoli M, Di Virgilio F, Abbracchio MP, Verderio C. (2006) A role for P2X7 in microglial proliferation. J Neurochem 99:745-758. Abstract

Adinolfi E, Callegari MG, Cirillo M, Pinton P, Giorgi C, Cavagna D, Rizzuto R and Di Virgilio F. (2009) Expression of the P2X7 receptor increases the Ca2+ content of the endoplasmic reticulum, activates NFATc1, and protects from apoptosis. J Biol Chem 284: 10120-8. Abstract

Di Virgilio F, Ferrari D, and Adinolfi E. (2009) P2X7: a growth-promoting receptor. Purinergic Signal in press.

View all comments by Francesco Di Virgilio

Excellent work by Williams and DeVirgilio. But what is the stimulant to the P2X7 receptor that stirs the immune cells in glia to activate from quiescence in AD?

View all comments by carmine palermo