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PMID: 15626823 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity.

Neuromolecular medicine ·Vol. 5 ·No. 3 ·2004-00-00 ·Pages 235-41

Gardian G, Yang L, Cleren C, Calingasan NY, Klivenyi P, Beal MF

Abstract

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.

MeSH Terms
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/antagonists & inhibitors Animals Brain/drug effects,enzymology,physiopathology Corpus Striatum/drug effects,metabolism,physiopathology Disease Models, Animal Dopamine/metabolism Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Immunohistochemistry Mice Neuroprotective Agents/pharmacology,therapeutic use Parkinsonian Disorders/drug therapy,metabolism,physiopathology Phenylbutyrates/pharmacology,therapeutic use Substantia Nigra/drug effects,metabolism,pathology Transcription, Genetic/drug effects,physiology Treatment Outcome Tyrosine 3-Monooxygenase/metabolism
Chemicals
Histone Deacetylase Inhibitors Neuroprotective Agents Phenylbutyrates 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Tyrosine 3-Monooxygenase Histone Deacetylases Dopamine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gardian Gabriella
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York-Presbyterian Hospital, 525 East 68th Street, Room F610, New York, NY 10021, USA.
Yang Lichuan
Cleren Carine
Calingasan Noel Y
Klivenyi Peter
Beal M Flint
References (26)
26 references, click to expand
  1. Effects of histone acetylation on transcriptional regulation of manganese superoxide dismutase gene.
    Biochem Biophys Res Commun. 2002 Jul 5;295(1):187-92 PMID: 12083788
  2. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila.
    Nature. 2001 Oct 18;413(6857):739-43 PMID: 11607033
  3. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.
    Hum Mol Genet. 2004 Jun 1;13(11):1183-92 PMID: 15102712
  4. The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms.
    Genes Dev. 1999 Oct 1;13(19):2570-80 PMID: 10521401
  5. Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy.
    Mol Cell Biol. 2003 Jan;23(2):744-53 PMID: 12509471
  6. Mitochondrial deficiency and cardiac sudden death in mice lacking the MEF2A transcription factor.
    Nat Med. 2002 Nov;8(11):1303-9 PMID: 12379849
  7. Kynurenine pathway measurements in Huntington's disease striatum: evidence for reduced formation of kynurenic acid.
    J Neurochem. 1990 Oct;55(4):1327-39 PMID: 2144582
  8. Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5.
    Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14400-5 PMID: 11114197
  9. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans.
    Nature. 2001 Mar 8;410(6825):227-30 PMID: 11242085
  10. SIRT3, a human SIR2 homologue, is an NAD-dependent deacetylase localized to mitochondria.
    Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8 PMID: 12374852
  11. 3-Nitropropionic acid neurotoxicity is attenuated in copper/zinc superoxide dismutase transgenic mice.
    J Neurochem. 1995 Aug;65(2):919-22 PMID: 7616254
  12. Regulation of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha ) and mitochondrial function by MEF2 and HDAC5.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1711-6 PMID: 12578979
  13. Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator.
    Endocr Rev. 2003 Feb;24(1):78-90 PMID: 12588810
  14. Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4.
    J Biol Chem. 2000 Jul 21;275(29):22563-7 PMID: 10825153
  15. Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex.
    J Neurol Sci. 1992 Mar;108(1):80-7 PMID: 1385624
  16. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease.
    Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2041-6 PMID: 12576549
  17. Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway.
    Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4281-6 PMID: 12640146
  18. A novel action of histone deacetylase inhibitors in a protein aggresome disease model.
    Curr Biol. 2004 Mar 23;14 (6):488-92 PMID: 15043813
  19. The antitumor histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits antiinflammatory properties via suppression of cytokines.
    Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):2995-3000 PMID: 11867742
  20. Treatment of spinal muscular atrophy by sodium butyrate.
    Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9808-13 PMID: 11504946
  21. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice.
    J Neurosci. 2003 Oct 15;23(28):9418-27 PMID: 14561870
  22. Involvement of oxidative stress in 3-nitropropionic acid neurotoxicity.
    Neurochem Int. 1996 Aug;29(2):167-71 PMID: 8837046
  23. Life extension in Drosophila by feeding a drug.
    Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):838-43 PMID: 11792861
  24. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK.
    Science. 2002 Apr 12;296(5566):349-52 PMID: 11951046
  25. Valproic acid, a mood stabilizer and anticonvulsant, protects rat cerebral cortical neurons from spontaneous cell death: a role of histone deacetylase inhibition.
    FEBS Lett. 2003 May 8;542(1-3):74-8 PMID: 12729901
  26. Histone deacetylase inhibitors reduce polyglutamine toxicity.
    Proc Natl Acad Sci U S A. 2001 Dec 18;98 (26):15179-84 PMID: 11742087
Article Info
Journal
Neuromolecular medicine
Abbr.
Neuromolecular Med
ISSN
1535-1084
DOI
10.1385/NMM:5:3:235
Published
2004-00-00
Pages
235-41
Language
English
Region
United States
NLM ID
101135365
Subset
IM
Grants
NINDS NIH HHS · NS 39258 · United States
External Links
PubMed source DOI: 10.1385/NMM:5:3:235 View journal details
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