| First Author | Liu J | Year | 2023 |
| Journal | eNeuro | Volume | 10 |
| Issue | 11 | PubMed ID | 37903620 |
| Mgi Jnum | J:348171 | Mgi Id | MGI:7550144 |
| Doi | 10.1523/ENEURO.0422-23.2023 | Citation | Liu J, et al. (2023) Prevention of Alzheimer Pathology by Blocking Neuregulin Signaling on Microglia. eNeuro 10(11):ENEURO.0422-23.2023 |
| abstractText | Plaque formation, microglial activation, and synaptic loss are pathologic hallmarks of Alzheimer's disease; however, removing plaques has had little clinical benefit. Here, we show that neuregulin-1, a glial growth factor, induces inflammatory cytokines and promotes phagocytic activity in vitro and augments microglial activation and plaque formation in 5XFAD Alzheimer's mice. Brain-specific targeting of neuregulin-1 by intraventricular delivery of a novel neuregulin-1 fusion protein antagonist, GlyB4, significantly alters microglial morphology and function to a nonpathogenic morphology in early-stage 5XFAD mice and prevents plaques from forming. Once plaques have already formed, GlyB4 reduces new plaque formation and prevents synaptic loss. Selective, targeted disruption of neuregulin-1 signaling on brain microglia with GlyB4 could be a novel "upstream" approach to slow or stop disease progression in Alzheimer's disease. |
