NFκB-activated Astroglial Release of Complement C3 Compromises Neuronal Morphology and Function Associated with Alzheimer’s Disease
| Autor: | Giulio Taglialatela, David J Shim, Jennifer Rodriguez-Rivera, Allysa L. Cole, Hui Zheng, Joanna L. Jankowsky, Li Yang, Angie C.A. Chiang, Stephanie W. Fowler, Hong Lian, Hui-Chen Lu, Lu Sun |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
Neuroscience(all) Transgene Mice Transgenic Biology Article Amyloid beta-Protein Precursor Mice Alzheimer Disease medicine Animals Humans Receptor Neurons Microscopy Confocal Amyloid beta-Peptides General Neuroscience Antagonist NF-kappa B Brain Complement C3 NFKB1 medicine.disease Complement system Receptors Complement Astrocytes Alzheimer's disease Signal transduction Neuroscience Signal Transduction |
| Popis: | SummaryAbnormal 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. |
| Databáze: | OpenAIRE |
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