Glial cell-derived neurotrophic factor protects against proteasome inhibition-induced dopamine neuron degeneration by suppression of endoplasmic reticulum stress and caspase-3 activation

Xuping Li, Changgeng Peng, Ang Li, Ming Ming, Dehua Yang, Weidong Le

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Evidence has shown that ubiquitin proteasome system (UPS) impairment plays an important role in the dopamine (DA) neurodegeneration in Parkinson's disease (PD). It has been reported that application of proteasomal inhibitor lactacystin in ventral mesencephalon (VM) cultures can cause DA neurodegeneration, although the underlying mechanisms are not clear. Herein, we used the lactacystin-induced DA cell degeneration model to study the neuroprotection of glial cell-derived neurotrophic factor (GDNF) in VM cultures. We measured the expression of endoplasmic reticulum stress (ERS)-related genes, and determined the caspase-3 activation, apoptotic cell death, as well as α-synuclein- positive inclusions in DA neurons. We found that GDNF treatment significantly suppressed the expression of ERS-related genes and inhibited the activation of caspase-3 and apoptotic cell death without affecting α-synuclein-positive inclusions in DA neurons. Our study suggests that the protection of GDNF against DA neurodegeneration in the UPS impairment model is associated with ERS and caspase-3 suppression.

Original languageEnglish (US)
Pages (from-to)943-950
Number of pages8
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume62
Issue number9
DOIs
StatePublished - Sep 2007

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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