Loading…

Dephosphorylated rather than hyperphosphorylated Tau triggers a pro-inflammatory profile in microglia through the p38 MAPK pathway

Tauopathies are a broad set of neurodegenerative dementias characterized by the aggregation of Tau protein. Activated microglia and elevated levels of pro-inflammatory molecules are also pathological hallmarks of tauopathies. In these diseases, intracellular Tau is secreted to the extracellular spac...

Full description

Saved in:
Bibliographic Details
Published in:Experimental neurology 2018-12, Vol.310, p.14-21
Main Authors: Perea, Juan Ramón, Ávila, Jesús, Bolós, Marta
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tauopathies are a broad set of neurodegenerative dementias characterized by the aggregation of Tau protein. Activated microglia and elevated levels of pro-inflammatory molecules are also pathological hallmarks of tauopathies. In these diseases, intracellular Tau is secreted to the extracellular space, where it interacts with other cells, such as neurons and glia, promoting inflammation. However, the mechanism through which extracellular Tau triggers pro-inflammatory responses in microglia remains unknown. Primary microglia cultures were treated with extracellular Tau in its hyperphosphorylated, dephosphorylated or non-phosphorylated form. Protein cytokine arrays, real-time PCR, inhibition of the p38 MAPK pathway, phosphatase assays, and quantification of proteins through immunoblotting were used to analyze the effect of extracellular Tau on the pro-inflammatory response of microglia. The main finding of this work is that extracellular non-phosphorylated and dephosphorylated forms of Tau, rather than hyperphosphorylated Tau, activate the p38 MAPK pathway in microglia, thus triggering a pro-inflammatory response in these cells. [Display omitted] •Non-phosphorylated and dephosphorylated Tau activate the p38 pathway in microglia.•Microglial p38 is not activated in the presence of hyperphosphorylated Tau.•Tau treatment leads to an overproduction of pro-inflammatory cytokines by p38.•p38 inhibition suppresses microglia-induced inflammation triggered by Tau.
ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2018.08.007