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Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 mice
Wagner, Lisa K. ;  Gilling, Kate E. ;  Schormann, Eileen ;  Kloetzel, Peter M. ;  Heppner, Frank L. ;  Krueger, Elke ;  Prokop, Stefan

HaupttitelImmunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 mice
AutorWagner, Lisa K.
AutorGilling, Kate E.
AutorSchormann, Eileen
AutorKloetzel, Peter M.
AutorHeppner, Frank L.
AutorKrueger, Elke
AutorProkop, Stefan
Seitenzahl16 Seiten
DDC610 Medizin und Gesundheit
Auch erschienen inActa Neuropathologica CommunicationsNeuroscience of Disease. - 5 (2017), Artikel Nr. 52
ZusammenfassungThe immunoproteasome (iP) represents a specialized type of proteasomes, which plays an important role in the clearance of oxidant-damaged proteins under inflammatory and pathological conditions determining the outcome of various diseases. In Alzheimer’s disease (AD)-like APPPS1 mice Aβ-deposition is paralleled by iP upregulation, most likely mediated through type I interferon induction. To define the impact of increased iP expression we crossed APPPS1 mice with mice deficient in the iP subunit LMP7 resulting in impaired iP function. While LMP7 deficient APPPS1 mice showed no major change in cerebral Aβ-pathology, we observed an altered cytokine response in microglia isolated from LMP7 deficient APPPS1 mice compared to LMP7 expressing APPPS1 control mice. The altered microglial cytokine profile upon iP deficiency in the presence of extracellular Aβ-pathology was associated with an improvement of Aβ-associated cognitive deficits typically present in APPPS1 mice. Our findings suggest a role for iP in the regulation of the innate immune response towards extracellular Aβ-pathology and indicate that inhibition of iP function can modulate the cognitive phenotype upon overexpression of Aβ.
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Fachbereich/EinrichtungMedizinische Fakultät Charité - Universitätsmedizin Berlin
Erscheinungsjahr2017
Dokumententyp/-SammlungenWissenschaftlicher Artikel
SpracheEnglisch
RechteCreative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Anmerkungen des AutorsDer Artikel wurde in einer reinen Open-Access-Zeitschrift publiziert.
Erstellt am17.10.2017 - 12:22:48
Letzte Änderung17.10.2017 - 12:23:14
 
Statische URLhttp://edocs.fu-berlin.de/docs/receive/FUDOCS_document_000000028330
DOI10.1186/s40478-017-0453-5
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