CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
Author:
Mancuso Renzo1, Fryatt Gemma1, Cleal Madeleine1, Obst Juliane1, Pipi Elena1, Monzón-Sandoval Jimena23, Ribe Elena2, Winchester Laura2, Webber Caleb23, Nevado Alejo2, Jacobs Tom4, Austin Nigel4, Theunis Clara5, Grauwen Karolien5, Daniela Ruiz Eva1, Mudher Amrit1, Vicente-Rodriguez Marta6, Parker Christine A7, Simmons Camilla6, Cash Diana6, Richardson Jill8, Bullmore Edward T, Bhatti Junaid, Chamberlain Samuel J, Correia Marta M, Crofts Anna L, Dickinson Amber, Foster Andrew C, Kitzbichler Manfred G, Knight Clare, Lynall Mary-Ellen, Maurice Christina, O'Donnell Ciara, Pointon Linda J, Hyslop Peter St George, Turner Lorinda, Vertes Petra, Widmer Barry, Williams Guy B, Morgan B Paul, Leckey Claire A, Morgan Angharad R, O'Hagan Caroline, Touchard Samuel, Cavanagh Jonathan, Deith Catherine, Farmer Scott, McClean John, McColl Alison, McPherson Andrew, Scouller Paul, Sutherland Murray, Boddeke H W G M (Erik), Richardson Jill C, Khan Shahid, Murphy Phil, Parker Christine A, Patel Jai, Jones Declan, de Boer Peter, Kemp John, Drevets Wayne C, Nye Jeffrey S, Wittenberg Gayle, Isaac John, Bhattacharya Anindya, Carruthers Nick, Kolb Hartmuth, Pariante Carmine M, Turkheimer Federico, Barker Gareth J, Byrom Heidi, Cash Diana, Cattaneo Annamaria, Gee Antony, Hastings Caitlin, Mariani Nicole, McLaughlin Anna, Mondelli Valeria, Nettis Maria, Nikkheslat Naghmeh, Randall Karen, Sheridan Hannah, Simmons Camilla, Singh Nisha, Loo Victoria Van, Vicente-Rodriguez Marta, Wood Tobias C, Worrell Courtney, Zajkowska Zuzanna, Plath Niels, Egebjerg Jan, Eriksson Hans, Gastambide Francois, Adams Karen Husted, Jeggo Ross, Thomsen Christian, Pederson Jan Torleif, Campbell Brian, Möller Thomas, Nelson Bob, Zorn Stevin, O'Connor Jason, Attenburrow Mary Jane, Baird Alison, Benjamin Jithen, Clare Stuart, Cowen Philip, Huang I-Shu (Dante), Hurley Samuel, Jones Helen, Lovestone Simon, Mada Francisca, Nevado-Holgado Alejo, Oladejo Akintayo, Ribe Elena, Smith Katy, Vyas Anviti, Hughes Zoe, Balice-Gordon Rita, Duerr James, Piro Justin R, Sporn Jonathan, Hugh Perry (PI V, Cleal Madeleine, Fryatt Gemma, Gomez-Nicola Diego, Mancuso Renzo, Reynolds Richard, Harrison Neil A, Cercignani Mara, Clarke Charlotte L, Hoskins Elizabeth, Kohn Charmaine, Murray Rosemary, Wilcock Lauren, Wlazly Dominika, Mount Howard, Jones Declan N C9, Lovestone Simon210, Gómez-Nicola Diego1, Perry V Hugh1,
Affiliation:
1. Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK 2. Department of Physiology Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK 3. UK Dementia Research Institute, Cardiff University, Hadyn Ellis Building, Maindy Road, Cardiff, CF24 4HQ, UK 4. Janssen Research and Development, Turnhoutseweg 30, box 270, 2340 Beerse 1, Belgium 5. Janssen Neuroscience Research and Development, Janssen Pharmaceutical Companies of Johnson and Johnson, Turnhoutseweg 30, 2340, Beerse, Belgium 6. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK 7. Experimental Medicine Imaging, GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG1 2NY, UK 8. Neurosciences Therapeutic Area, GlaxoSmithKline R&D, Stevenage, UK 9. Janssen Neuroscience External Innovation, Johnson and Johnson Innovation Centre, One Chapel Place, London, W1G 0BG, UK 10. Oxford Health NHS Foundation Trust, Oxford, UK
Abstract
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.
Funder
Wellcome Trust NIHR Oxford Health Biomedical Research Centre
Publisher
Oxford University Press (OUP)
Subject
Neurology (clinical)
Cited by
148 articles.
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