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

doi:10.1016/j.neuron.2014.11.018

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

Neurology

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473 Scopus citations

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 language	English (US)
Pages (from-to)	101-115
Number of pages	15
Journal	Neuron
Volume	85
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2014.11.018
State	Published - Jan 7 2015

ASJC Scopus subject areas

General Neuroscience

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10.1016/j.neuron.2014.11.018

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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

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

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.",

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

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AU - Lian, Hong

AU - Yang, Li

AU - Cole, Allysa

AU - Sun, Lu

AU - Chiang, Angie C.A.

AU - Fowler, Stephanie W.

AU - Shim, David J.

AU - Rodriguez-Rivera, Jennifer

AU - Taglialatela, Giulio

AU - Jankowsky, Joanna L.

AU - Lu, Hui Chen

AU - Zheng, Hui

PY - 2015/1/7

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AB - 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.

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

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