IKKbeta Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology
Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Abeta clearance. However, studies examining innate immunity in Abeta pathology and ne...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2014
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| Sorozat: | JOURNAL OF NEUROSCIENCE
34 No. 39 |
| doi: | 10.1523/JNEUROSCI.1348-14.2014 |
| mtmt: | 2755871 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/10504 |
| LEADER | 02304nab a2200301 i 4500 | ||
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| 001 | publ10504 | ||
| 005 | 20190614132407.0 | ||
| 008 | 170210s2014 hu o 0|| zxx d | ||
| 022 | |a 0270-6474 | ||
| 024 | 7 | |a 10.1523/JNEUROSCI.1348-14.2014 |2 doi | |
| 024 | 7 | |a 2755871 |2 mtmt | |
| 040 | |a SZTE Publicatio Repozitórium |b hun | ||
| 041 | |a zxx | ||
| 100 | 1 | |a Liu Yang | |
| 245 | 1 | 0 | |a IKKbeta Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology |h [elektronikus dokumentum] / |c Liu Yang |
| 260 | |c 2014 | ||
| 300 | |a 12982-12999 | ||
| 490 | 0 | |a JOURNAL OF NEUROSCIENCE |v 34 No. 39 | |
| 520 | 3 | |a Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (Abeta) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Abeta clearance. However, studies examining innate immunity in Abeta pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKKbeta, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKbeta in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Abeta load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKbeta deficiency enhanced microglial recruitment to Abeta deposits and facilitated Abeta internalization, perhaps by inhibiting TGF-beta-SMAD2/3 signaling, but did not affect Abeta production and efflux. Therefore, inhibition of IKKbeta signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Abeta clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression. | |
| 700 | 0 | 1 | |a Liu Xu |e aut |
| 700 | 0 | 1 | |a Hao Wenlin |e aut |
| 700 | 0 | 1 | |a Decker Yann |e aut |
| 700 | 0 | 1 | |a Schomburg Robert |e aut |
| 700 | 0 | 1 | |a Fülöp Lívia |e aut |
| 700 | 0 | 1 | |a Pasparakis Manolis |e aut |
| 700 | 0 | 1 | |a Menger Michael D. |e aut |
| 700 | 0 | 1 | |a Fassbender Klaus |e aut |
| 856 | 4 | 0 | |u http://publicatio.bibl.u-szeged.hu/10504/1/Liu_JNeurosci_2014.pdf |z Dokumentum-elérés |