作者
Renzo Mancuso, Gemma Fryatt, Madeleine Cleal, Juliane Obst, Elena Pipi, Jimena Monzón-Sandoval, Elena Ribe, Laura Winchester, Caleb Webber, Alejo Nevado, Tom Jacobs, Nigel Austin, Clara Theunis, Karolien Grauwen, Eva Daniela Ruiz, Amrit Mudher, Marta Vicente-Rodriguez, Christine A Parker, Camilla Simmons, Diana Cash, Jill Richardson, Declan NC Jones, Simon Lovestone, Diego Gómez-Nicola, V Hugh Perry
发表日期
2019/10/1
期刊
Brain
卷号
142
期号
10
页码范围
3243-3264
出版商
Oxford University Press
简介
Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and …
学术搜索中的文章
CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice
R Mancuso, G Fryatt, M Cleal, J Obst, E Pipi… - Brain, 2019