Artikel
IL-12/IL-23 signalling in Alzheimer’s disease
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Autoren
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Pascale Eede
- Charité Universitätsmedizin Berlin, Institute of Neuropathology, Berlin, Germany
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Juliane Obst
- Charité Universitätsmedizin Berlin, Institute of Neuropathology, Berlin, Germany
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Burkhard Becher
- University of Zurich, Division of Neuroimmunology, Institute of Experimental Immunology, Zurich, Switzerland
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Stefan Prokop
- Charité Universitätsmedizin Berlin, Institute of Neuropathology, Berlin, Germany
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Frank Heppner
- Charité Universitätsmedizin Berlin, Institute of Neuropathology, Berlin, Germany
| Veröffentlicht: | 25. August 2015 |
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Gliederung
Text
Alzheimer’s disease (AD) pathology displays an inflammatory component characterized by the presence of pro-inflammatory cytokines particularly in response to β-amyloid (Aβ). Previously we have shown that APPPS1 mice deficient in p40 (Il12b-/-), the essential subunit of both interleukin- (IL-) 12 and IL-23, exhibit a markedly reduced Aβ plaque burden compared to p40 expressing control littermates [1]. In addition, treatment of APPPS1 mice with a p40 neutralizing antibody ameliorates cognitive function and reduces soluble Aβ levels.
When elucidating the precise mechanism of Aβ reduction and amelioration of cognitive symptoms upon absence of p40- mediated signaling, we identified microglia as the key source of p40, while astrocytes were found, in vitro, to express the prominent downstream mediator of both IL-12 and IL-23, STAT4, as well as IL-12 receptor subunits in the brain of APPPS1 mice. Subsequent experiments aimed to characterize functional properties of the aforementioned cells in the presence or absence of either p40 or its receptor, with a specific focus on Aβ production and Aβ clearance, are supposed to identify distinct IL-12/23-dependent mechanisms for therapeutic modulation of AD pathology.
References
- 1.
- Vom Berg J, Prokop S, Miller KR, Obst J, et al. Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease–like pathology and cognitive decline. Nat Med. 2012 Dec 6;18(12):1812-9.
