Role of protein phosphatases and mitochondria in the neuroprotective effects of estrogens

James W. Simpkins, Kun Don Yi, Shao Hua Yang

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


In the present treatise, we provide evidence that the neuroprotective and mito-protective effects of estrogens are inexorably linked and involve the ability of estrogens to maintain mitochondrial function during neurotoxic stress. This is achieved by the induction of nuclear and mitochondrial gene expression, the maintenance of protein phosphatases levels in a manner that likely involves modulation of the phosphorylation state of signaling kinases and mitochondrial pro- and anti-apoptotic proteins, and the potent redox/antioxidant activity of estrogens. These estrogen actions are mediated through a combination of estrogens receptor (ER)-mediated effects on nuclear and mitochondrial transcription of protein vital to mitochondrial function, ER-mediated, non-genomic signaling and non-ER-mediated effects of estrogens on signaling and oxidative stress. Collectively, these multifaceted, coordinated action of estrogens leads to their potency in protecting neurons from a wide variety of acute insults as well as chronic neurodegenerative processes.

Original languageEnglish
Pages (from-to)93-105
Number of pages13
JournalFrontiers in Neuroendocrinology
Issue number2
StatePublished - Jul 2009


  • 17β-Estradiol
  • Estrogen receptors
  • Estrogens
  • Mitochondria
  • Neuroprotection
  • Non-feminizing estrogens
  • Protein phosphatases


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