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

Research output: Contribution to journalArticle

116 Citations (Scopus)

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)101-116
Number of pages16
JournalNeuron
Volume85
Issue number1
DOIs
StatePublished - Jan 7 2015

Fingerprint

Complement C3
Alzheimer Disease
Brain
Neuroglia
Transgenic Mice
Complement System Proteins
Neurons
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease. / Lian, Hong; Yang, Li; Cole, Allysa; Sun, Lu; Chiang, Angie C A; Fowler, Stephanie W.; Shim, David J.; Rodriguez-Rivera, Jennifer; Taglialatela, Giulio; Jankowsky, Joanna L.; Lu, Hui Chen; Zheng, Hui.

In: Neuron, Vol. 85, No. 1, 07.01.2015, p. 101-116.

Research output: Contribution to journalArticle

Lian, H, Yang, L, Cole, A, Sun, L, Chiang, ACA, Fowler, SW, Shim, DJ, Rodriguez-Rivera, J, Taglialatela, G, Jankowsky, JL, Lu, HC & Zheng, H 2015, 'NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease', Neuron, vol. 85, no. 1, pp. 101-116. https://doi.org/10.1016/j.neuron.2014.11.018
Lian, Hong ; Yang, Li ; Cole, Allysa ; Sun, Lu ; Chiang, Angie C A ; Fowler, Stephanie W. ; Shim, David J. ; Rodriguez-Rivera, Jennifer ; Taglialatela, Giulio ; Jankowsky, Joanna L. ; Lu, Hui Chen ; Zheng, Hui. / NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease. In: Neuron. 2015 ; Vol. 85, No. 1. pp. 101-116.
@article{2f466d64491b4ebeb6340b3934f808f1,
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",
year = "2015",
month = "1",
day = "7",
doi = "10.1016/j.neuron.2014.11.018",
language = "English (US)",
volume = "85",
pages = "101--116",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - NFκB-Activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer's Disease

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

Y1 - 2015/1/7

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84920841382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84920841382&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2014.11.018

DO - 10.1016/j.neuron.2014.11.018

M3 - Article

C2 - 25533482

AN - SCOPUS:84920841382

VL - 85

SP - 101

EP - 116

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 1

ER -