Divergent effect of proteasome inhibition on interleukin-1beta and tumor necrosis factor alpha signaling in human astroglial cells.

Abstract:

:Impaired functioning of the proteasome pathway is one of the molecular mechanism underlying neurodegenerative changes in Alzheimer's disease. In this study, we report that dysfunction of the proteasome pathway in astroglial cells leads to decreased survival and dysregulation of chemokines by differential regulation of the nuclear factor kappa B and c-jun N-terminal kinase (JNK) pathways. We further demonstrated that proteasome inhibition augmented interleukin-1 beta- and tumor necrosis factor-alpha-induced activation of the IkappaBalpha kinase and MKK4/JNK/c-Jun pathway along with TAK1 activation. These results suggest that impaired function of the proteasome pathway may potentiate the immuno-pathologic role of secondarily activated astrocytes in the brain.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Choi K,Lee J,Choi C

doi

10.1016/j.febslet.2007.08.065

subject

Has Abstract

pub_date

2007-10-02 00:00:00

pages

4691-6

issue

24

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(07)00947-7

journal_volume

581

pub_type

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