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


ABSTRACT: Abnormal NF?B activation has been implicated in Alzheimer's disease (AD). However, the signaling pathways governing NF?B regulation and function in the brain are poorly understood. We identify complement protein C3 as an astroglial target of NF?B and show that C3 release acts through neuronal C3aR to disrupt dendritic morphology and network function. Exposure to A? activates astroglial NF?B 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 NF?B/C3/C3aR signaling may contribute to synaptic dysfunction in AD, and C3aR antagonists may be therapeutically beneficial.

SUBMITTER: Lian H 

PROVIDER: S-EPMC4289109 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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

Lian Hong H   Yang Li L   Cole Allysa A   Sun Lu L   Chiang Angie C-A AC   Fowler Stephanie W SW   Shim David J DJ   Rodriguez-Rivera Jennifer J   Taglialatela Giulio G   Jankowsky Joanna L JL   Lu Hui-Chen HC   Zheng Hui H  

Neuron 20141218 1


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  ...[more]

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