Prevention of Alzheimer Pathology by Blocking Neuregulin Signaling on Microglia.
eNeuro
; 10(11)2023 11.
Article
em En
| MEDLINE
| ID: mdl-37903620
ABSTRACT
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article