Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity
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. The...
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| Veröffentlicht in: | Neuromolecular medicine 2004-01, Vol.5 (3), p.235-242 |
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| creator | Gardian, Gabriella Yang, Lichuan Cleren, Carine Calingasan, Noel Y Klivenyi, Peter Beal, M Flint |
| description | 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. |
| doi_str_mv | 10.1385/nmm:5:3:235 |
| format | Article |
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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. 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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. 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| subjects | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - antagonists & inhibitors Animals Brain - drug effects Brain - enzymology Brain - physiopathology Corpus Striatum - drug effects Corpus Striatum - metabolism Corpus Striatum - physiopathology Disease Models, Animal Dopamine - metabolism Histone Deacetylase Inhibitors Histone Deacetylases - metabolism Immunohistochemistry Mice Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use Parkinson's disease Parkinsonian Disorders - drug therapy Parkinsonian Disorders - metabolism Parkinsonian Disorders - physiopathology Phenylbutyrates - pharmacology Phenylbutyrates - therapeutic use Proteins Substantia Nigra - drug effects Substantia Nigra - metabolism Substantia Nigra - pathology Transcription, Genetic - drug effects Transcription, Genetic - physiology Treatment Outcome Tyrosine 3-Monooxygenase - metabolism |
| title | Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity |
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