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. 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.
Gardian
Gabriella
G
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
L
Cleren
Carine
C
Calingasan
Noel Y
NY
Klivenyi
Peter
P
Beal
M Flint
MF
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010654:Phenylbutyrates / Q000494:pharmacology* / Q000627:therapeutic use; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D018696:Neuroprotective Agents; D010654:Phenylbutyrates; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D006655:Histone Deacetylases; D004298:Dopamine