NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease

Hong Lian, Li Yang, Allysa Cole, Lu Sun, Angie C.A. Chiang, Stephanie W. Fowler, David J. Shim, Jennifer Rodriguez-Rivera, Giulio Taglialatela, Joanna L. Jankowsky, Hui Chen Lu, Hui Zheng

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Abstract

Abnormal NFκB activation has been implicated in Alzheimer's disease (AD). However, the signaling pathways governing NFκB regulation and function in the brain are poorly understood. We identify complement protein C3 as an astroglial target of NFκB and show that C3 release acts through neuronal C3aR to disrupt dendritic morphology and network function. Exposure to Aβ activates astroglial NFκB and C3 release, consistent with the high levels of C3 expression in brain tissue from AD patients and APP transgenic mice, where C3aR antagonist treatment rescues cognitive impairment. Therefore, dysregulation of neuron-glia interaction through NFκB/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial.

Original languageEnglish (US)
Pages (from-to)101-115
Number of pages15
JournalNeuron
Volume85
Issue number1
DOIs
StatePublished - Jan 7 2015

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lian, H., Yang, L., Cole, A., Sun, L., Chiang, A. C. A., Fowler, S. W., Shim, D. J., Rodriguez-Rivera, J., Taglialatela, G., Jankowsky, J. L., Lu, H. C., & Zheng, H. (2015). NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease. Neuron, 85(1), 101-115. https://doi.org/10.1016/j.neuron.2014.11.018