title: Neuroprotective effects of oral administration of triacetyluridine against MPTP neurotoxicity.
abstract: Administration of triacetyluridine (TAU) is a means of delivering exogenous pyrimidines to the brain, which may help to compensate for bioenergetic defects. TAU has previously been shown to be neuroprotective in animal models of Huntington's and Alzheimer's diseases. We examined whether oral administration of TAU in the diet could exert significant neuroprotective effects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity model of Parkinson's disease. Administration of TAU significantly attenuated MPTP-induced depletion of striatal dopamine and loss of tyrosine-hydroxylase-positive neurons in the substantia nigra. These findings suggest that administration of TAU may be a novel approach for treating neurodegenerative diseases associated with impaired mitochondrial function.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College, Cornell University, New York-Presbyterian Hospital, New York, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Klivenyi
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gardian
authors.forename: Noel Y
authors.initials: NY
authors.lastname: Calingasan
authors.forename: Lichuan
authors.initials: L
authors.lastname: Yang
authors.forename: Reid
authors.initials: R
authors.lastname: von Borstel
authors.forename: Joel
authors.initials: J
authors.lastname: Saydoff
authors.forename: Susan E
authors.initials: SE
authors.lastname: Browne
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000085:Acetates; D000818:Animals; D019587:Dietary Supplements; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000517:prevention & control; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D014529:Uridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000085:Acetates; D018696:Neuroprotective Agents; D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; C000609666:uridine triacetate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D014529:Uridine; D006719:Homovanillic Acid