Creatine and cyclocreatine attenuate MPTP neurotoxicity

Russell T. Matthews, Robert J. Ferrante, P. Klivényi, Lichuan Yang, Autumn M. Klein, Gerald Mueller, Rima Kaddurah-Daouk, M. Flint Beal

Research output: Contribution to journalArticle

285 Citations (Scopus)

Abstract

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 cyclo-phosphocreatine (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.

Original languageEnglish
Pages (from-to)142-149
Number of pages8
JournalExperimental Neurology
Volume157
Issue number1
DOIs
Publication statusPublished - May 1999

Fingerprint

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Creatine
Phosphocreatine
1-Methyl-4-phenylpyridinium
Electron Transport Complex I
Monoamine Oxidase
Tyrosine 3-Monooxygenase
Parkinsonian Disorders
Neuroprotective Agents
Substantia Nigra
Creatine Kinase
Parkinson Disease
cyclocreatine
Dopamine
Buffers
Adenosine Triphosphate
Neurons

Keywords

  • Creatine
  • Cyclocreatine
  • Free radicals
  • Mitochondria
  • MPTP
  • Parkinson's
  • Phosphocreatine

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Matthews, R. T., Ferrante, R. J., Klivényi, P., Yang, L., Klein, A. M., Mueller, G., ... Beal, M. F. (1999). Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology, 157(1), 142-149. https://doi.org/10.1006/exnr.1999.7049

Creatine and cyclocreatine attenuate MPTP neurotoxicity. / Matthews, Russell T.; Ferrante, Robert J.; Klivényi, P.; Yang, Lichuan; Klein, Autumn M.; Mueller, Gerald; Kaddurah-Daouk, Rima; Beal, M. Flint.

In: Experimental Neurology, Vol. 157, No. 1, 05.1999, p. 142-149.

Research output: Contribution to journalArticle

Matthews, RT, Ferrante, RJ, Klivényi, P, Yang, L, Klein, AM, Mueller, G, Kaddurah-Daouk, R & Beal, MF 1999, 'Creatine and cyclocreatine attenuate MPTP neurotoxicity', Experimental Neurology, vol. 157, no. 1, pp. 142-149. https://doi.org/10.1006/exnr.1999.7049
Matthews RT, Ferrante RJ, Klivényi P, Yang L, Klein AM, Mueller G et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology. 1999 May;157(1):142-149. https://doi.org/10.1006/exnr.1999.7049
Matthews, Russell T. ; Ferrante, Robert J. ; Klivényi, P. ; Yang, Lichuan ; Klein, Autumn M. ; Mueller, Gerald ; Kaddurah-Daouk, Rima ; Beal, M. Flint. / Creatine and cyclocreatine attenuate MPTP neurotoxicity. In: Experimental Neurology. 1999 ; Vol. 157, No. 1. pp. 142-149.
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