In vitro and in vivo neuroprotection by γ-glutamylcysteine ethyl ester against MPTP: Relevance to the role of glutathione in Parkinson's disease

Shankar J. Chinta, Subramanian Rajagopalan, D. Allan Butterfield, Julie K. Andersen

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Glutathione is an abundant intracellular thiol antioxidant whose levels are reduced both in Parkinson's disease itself and in a widely used animal model of the disorder, systemic MPTP administration. Previous in vitro work from our laboratory has suggested that glutathione depletion may be directly responsible for mitochondrial dysfunction, which ultimately leads to dopaminergic cell death associated with the disease. Here, we demonstrate the ability of gamma-glutamylcysteine ethyl ester, a lipid permeable derivative of the major substrate for scavenger glutathione synthesis, to counteract glutathione loss and neurodegeneration associated with in vitro and in vivo administration of MPTP or its derivatives. This data suggests that prevention of glutathione depletion is a likely therapeutic target for the disease.

Original languageEnglish
Pages (from-to)137-141
Number of pages5
JournalNeuroscience Letters
Volume402
Issue number1-2
DOIs
StatePublished - Jul 10 2006

Bibliographical note

Funding Information:
This work was supported in part by NIH grants to D.A.B. [AG-10836; AG-05119] and to J.A. [AG-12141 and NS-045615].

Keywords

  • Glutathione
  • MPTP
  • Parkinson's disease
  • Tyrosine hydroxylase
  • γ-Glutamylcysteinyl ethyl ester

ASJC Scopus subject areas

  • Neuroscience (all)

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