Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity

Gabriella Gardian, Lichuan Yang, Carine Cleren, Noel Y. Calingasan, Peter Klivenyi, M. Flint Beal

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71 Citations (Scopus)


There is increasing evidence that administration of histone deacetylase (HDAC) inhibitors can exert neuroprotective effects by a variety of mechanisms. Phenylbutyrate is a well-known HDAC inhibitor, which increases gene transcription of a number of genes, and also exerts neuroprotective effects. These include several antioxidant enzymes, chaperones, and genes involved in cell survival. We examined whether administration of phenylbutyrate could exert significant neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP), which has been used to model Parkinson's disease. Administration of phenylbutyrate significantly attenuated MPTP-induced depletion of striatal dopamine and loss of tyrosine hydroxylase-positive neurons in the substantia nigra. These findings provide further evidence that administration of phenylbutyrate may be a useful approach for the treatment of neurodegenerative diseases.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalNeuroMolecular Medicine
Issue number3
Publication statusPublished - Dec 1 2004


  • Gene transcription
  • Histone acetylation
  • MPTP
  • Parkinson's disease
  • Phenylbutynate

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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  • Cite this

    Gardian, G., Yang, L., Cleren, C., Calingasan, N. Y., Klivenyi, P., & Beal, M. F. (2004). Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. NeuroMolecular Medicine, 5(3), 235-241.