Neuroprotection by iron chelator against proteasome inhibitor-induced nigral degeneration

Xiong Zhang, Wenjie Xie, Shen Qu, Tianhong Pan, Xiaotong Wang, Weidong Le

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The cause of the neurodegenerative process in Parkinson's disease (PD) remains unclear, but evidence suggests that failure of the ubiquitin-proteasome system may play a major role in the pathogenesis of the disease. Iron is believed to be a key contributor to PD pathology by inducing aggregation of α-synuclein and by generating oxidative stress. Our present studies have shown that micro-injection of the proteasome inhibitor lactacystin into the substantia nigra (SN) of C57BL/6 mice causes significant loss of dopaminergic cells and induces intracellular inclusion body formation. We have also found that co-injection of the iron chelator desferrioxamine not only attenuates the lactacystin-induced dopamine neuron loss, but also reduces the presence of ubiquitin-positive intracellular inclusions in the SN, whereas use of iron-deficient diet has no such protective effects. These results may support that iron plays a key role in proteasome inhibitor-induced nigral pathology and that reducing iron reactivity may prevent dopaminergic neuron degeneration and reduce abnormal protein aggregation.

Original languageEnglish (US)
Pages (from-to)544-549
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume333
Issue number2
DOIs
StatePublished - Jul 29 2005

Keywords

  • Dopaminergic cells
  • Iron
  • Iron chelator
  • Neuroprotection
  • Parkinson's disease
  • Proteasome inhibitor
  • Ubiquitin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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