Creatine and cyclocreatine attenuate MPTP neurotoxicity.

Journal Article (Journal Article)

Systemic administration of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) produces parkinsonism in experimental animals by a mechanism involving impaired energy production. MPTP is converted by monoamine oxidase B to 1-methyl-4-phenylpyridinium (MPP+), which blocks complex I of the electron transport chain. Oral supplementation with creatine or cyclocreatine, which are substrates for creatine kinase, may increase phosphocreatine (PCr) or cyclophosphocreatine (PCCr) and buffer against ATP depletion and thereby exert neuroprotective effects. In the present study we found that oral supplementation with either creatine or cyclocreatine produced significant protection against MPTP-induced dopamine depletions in mice. Creatine protected against MPTP-induced loss of Nissl and tyrosine hydroxylase immunostained neurons in the substantia nigra. Creatine and cyclocreatine had no effects on the conversion of MPTP to MPP+ in vivo. These results further implicate metabolic dysfunction in MPTP neurotoxicity and suggest a novel therapeutic approach, which may have applicability for Parkinson's disease.

Full Text

Duke Authors

Cited Authors

  • Matthews, RT; Ferrante, RJ; Klivenyi, P; Yang, L; Klein, AM; Mueller, G; Kaddurah-Daouk, R; Beal, MF

Published Date

  • May 1999

Published In

Volume / Issue

  • 157 / 1

Start / End Page

  • 142 - 149

PubMed ID

  • 10222117

International Standard Serial Number (ISSN)

  • 0014-4886

Digital Object Identifier (DOI)

  • 10.1006/exnr.1999.7049


  • eng

Conference Location

  • United States