CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Mancuso R., Fryatt G., Cleal M., Obst J., Pipi E., Monzón-Sandoval J., Ribe E., Winchester L., Webber C., Nevado A., Jacobs T., Austin N., Theunis C., Grauwen K., Daniela Ruiz E., Mudher A., Vicente-Rodriguez M., Parker CA., Simmons C., Cash D., Richardson J., Bullmore ET., Bhatti J., Chamberlain SJ., Correia MM., Crofts AL., Dickinson A., Foster AC., Kitzbichler MG., Knight C., Lynall M-E., Maurice C., O'Donnell C., Pointon LJ., Hyslop PSG., Turner L., Vertes P., Widmer B., Williams GB., Morgan BP., Leckey CA., Morgan AR., O'Hagan C., Touchard S., Cavanagh J., Deith C., Farmer S., McClean J., McColl A., McPherson A., Scouller P., Sutherland M., Boddeke HWGME., Richardson JC., Khan S., Murphy P., Parker CA., Patel J., Jones D., de Boer P., Kemp J., Drevets WC., Nye JS., Wittenberg G., Isaac J., Bhattacharya A., Carruthers N., Kolb H., Pariante CM., Turkheimer F., Barker GJ., Byrom H., Cash D., Cattaneo A., Gee A., Hastings C., Mariani N., McLaughlin A., Mondelli V., Nettis M., Nikkheslat N., Randall K., Sheridan H., Simmons C., Singh N., Loo VV., Vicente-Rodriguez M., Wood TC., Worrell C., Zajkowska Z., Plath N., Egebjerg J., Eriksson H., Gastambide F., Adams KH., Jeggo R., Thomsen C., Pederson JT., Campbell B., Möller T., Nelson B., Zorn S., O'Connor J., Attenburrow MJ., Baird A., Benjamin J., Clare S., Cowen P., Huang I-SD., Hurley S., Jones H., Lovestone S., Mada F., Nevado-Holgado A., Oladejo A., Ribe E., Smith K., Vyas A., Hughes Z., Balice-Gordon R., Duerr J., Piro JR., Sporn J., Hugh Perry (PI V., Cleal M., Fryatt G., Gomez-Nicola D., Mancuso R., Reynolds R., Harrison NA., Cercignani M., Clarke CL., Hoskins E., Kohn C., Murray R., Wilcock L., Wlazly D., Mount H., Jones DNC., Lovestone S., Gómez-Nicola D., Perry VH.
Microglia have been implicated in amyloid beta-induced neuropathology, but their role in tau-induced neurodegeneration remains unclear. Mancuso et al. report that blockade of microglial proliferation by CSF1R inhibitor JNJ-40346527 modifies brain inflammation and ameliorates disease progression in P301S tauopathy mice. CSF1R inhibition may have therapeutic potential in tau-mediated neurodegenerative diseases.