GDNF regulates the Aβ-induced endoplasmic reticulum stress response in rabbit hippocampus by inhibiting the activation of gadd 153 and the JNK and ERK kinases

Ghribi Othman, Mary M. Herman, Patcharin Pramoonjago, Natalie K. Spaulding, John Savory

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a potent survival agent for neurons, however, its effect on Aβ-evoked neuronal death has not been examined. We show that the injection of Aβ into New Zealand white rabbit brain activates the endoplasmic reticulum (ER) chaperones, grp 78 and grp 94, and the transcription factor, gadd 153. These effects correlate with the activation of JNK and ERK as well as of microglia and with the phosphorylation of tau protein. Treatment with GDNF inhibits the activation of gadd 153, reduces the phosphorylation of JNK, abolishes the phosphorylation of ERK, prevents microglial activation, greatly reduces apoptotic cells, and does not affect the phosphorylation of tau. Our data suggest that the tau hyperphosphorylation and apoptosis triggered by Aβ are two independent events, and that the neuroprotective effect of GDNF against Aβ may result either directly by the inhibition of ER stress or indirectly through the inhibition of JNK and ERK activation.

Original languageEnglish (US)
Pages (from-to)417-427
Number of pages11
JournalNeurobiology of Disease
Volume16
Issue number2
DOIs
StatePublished - Jul 1 2004

Fingerprint

MAP Kinase Kinase 4
Glial Cell Line-Derived Neurotrophic Factor
Endoplasmic Reticulum Stress
Hippocampus
Phosphorylation
Rabbits
tau Proteins
Microglia
Neuroprotective Agents
Endoplasmic Reticulum
Transcription Factors
Apoptosis
Neurons
Injections
Brain

Keywords

  • ERK
  • Endoplasmic reticulum
  • GDNF
  • JNK
  • Tau
  • gadd 153
  • grp 78
  • grp 94

ASJC Scopus subject areas

  • Neurology

Cite this

GDNF regulates the Aβ-induced endoplasmic reticulum stress response in rabbit hippocampus by inhibiting the activation of gadd 153 and the JNK and ERK kinases. / Othman, Ghribi; Herman, Mary M.; Pramoonjago, Patcharin; Spaulding, Natalie K.; Savory, John.

In: Neurobiology of Disease, Vol. 16, No. 2, 01.07.2004, p. 417-427.

Research output: Contribution to journalArticle

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