Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease

Oct 11, 2011Cellular and molecular life sciences : CMLS

Increasing and activating a key energy regulator helps protect dopamine neurons in a mouse model of Parkinson's disease

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Abstract

Transgenic mice overexpressing PGC-1α in dopaminergic neurons show increased resistance to cell degeneration induced by the neurotoxin MPTP.

  • Elevated levels of mitochondrial antioxidants SOD2 and Trx2 were observed in the substantia nigra of transgenic mice.
  • PGC-1α overexpression provided protection against MPTP-induced loss of dopamine in the striatum.
  • Mitochondria from PGC-1α transgenic mice exhibited an increased respiratory control ratio compared to wild-type animals.
  • The small molecule compound resveratrol (RSV) activated PGC-1α and protected dopaminergic neurons against MPTP-induced cell degeneration.
  • In vitro studies indicated that RSV enhanced PGC-1α gene transcription and increased levels of SOD2 and Trx2 through the activation of SIRT1.

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