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.
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Houston, TX 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Lian
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA.
authors.forename: Allysa
authors.initials: A
authors.lastname: Cole
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Angie C-A
authors.initials: AC
authors.lastname: Chiang
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Fowler
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Shim
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rodriguez-Rivera
authors.affiliation: Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Taglialatela
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Jankowsky
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine and the Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, TX 77030, USA.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Lu
authors.affiliation: Huffington Center on Aging, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: huiz@bcm.edu.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011951:Receptors, Complement / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D003176:Complement C3; D016328:NF-kappa B; D011951:Receptors, Complement; C085567:complement C3a receptor