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Neuron. 2015 Jan 7;85(1):101-115. doi: 10.1016/j.neuron.2014.11.018. Epub 2014 Dec 18.

NFκB-activated astroglial release of complement C3 compromises neuronal morphology and function associated with Alzheimer's disease.

Author information

1
Huffington Center on Aging, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Houston, TX 77030, USA.
2
Huffington Center on Aging, Houston, TX 77030, USA.
3
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
4
Huffington Center on Aging, Houston, TX 77030, USA; Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
5
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
6
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.
7
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.

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.

Comment in

PMID:
25533482
PMCID:
PMC4289109
DOI:
10.1016/j.neuron.2014.11.018
[Indexed for MEDLINE]
Free PMC Article

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