Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 miceReportar como inadecuado




Immunoproteasome deficiency alters microglial cytokine response and improves cognitive deficits in Alzheimer’s disease-like APPPS1 mice - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Acta Neuropathologica Communications

, 5:52

First Online: 24 June 2017Received: 05 June 2017Accepted: 06 June 2017DOI: 10.1186-s40478-017-0453-5

Cite this article as: Wagner, L.K., Gilling, K.E., Schormann, E. et al. acta neuropathol commun 2017 5: 52. doi:10.1186-s40478-017-0453-5

Abstract

The 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.

KeywordsProteasome Immunoproteasome Microglia Inflammation Alzheimer’s disease 



Autor: Lisa K. Wagner - Kate E. Gilling - Eileen Schormann - Peter M. Kloetzel - Frank L. Heppner - Elke Krüger - Stefan Prok

Fuente: https://link.springer.com/







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