X-Message-Number: 11953
Date: Sun, 13 Jun 1999 12:56:47 -0700 (PDT)
From: Doug Skrecky <>
Subject: neuroprotection with creatine

Authors
  Matthews RT.  Yang L.  Jenkins BG.  Ferrante RJ.  Rosen BR.  Kaddurah-Daouk
  R.  Beal MF.
Institution
  Neurochemistry Laboratory, Neurology Service and Massachusetts General
  Hospital Nuclear Magnetic Resonance Center, Department of Radiology,
  Massachusetts General Hospital and Harvard Medical School, Boston,
  Massachusetts 02114, USA.
Title
  Neuroprotective effects of creatine and
  cyclocreatine in animal models of Huntington's disease.
Source
  Journal of Neuroscience.  18(1):156-63, 1998 Jan 1.
Abstract
  The gene defect in Huntington's disease (HD) may result in an impairment of
  energy metabolism. Malonate and 3-nitropropionic acid (3-NP) are inhibitors
  of succinate dehydrogenase that produce energy depletion and lesions that
  closely resemble those of HD. Oral supplementation with creatine or
  cyclocreatine, which are substrates for the enzyme creatine kinase, may
  increase phosphocreatine (PCr) or phosphocyclocreatine (PCCr) levels and ATP
  generation and thereby may exert neuroprotective
  effects. We found that oral supplementation with either
  creatine or cyclocreatine produced significant protection against malonate
  lesions, and that creatine but not cyclocreatine supplementation
  significantly protected against 3-NP neurotoxicity. Creatine and
  cyclocreatine increased brain concentrations of PCr and PCCr, respectively,
  and creatine protected against depletions of PCr and ATP produced by 3-NP.
  Creatine supplementation protected against 3-NP induced increases in striatal
  lactate concentrations in vivo as assessed by 1H magnetic resonance
  spectroscopy. Creatine and cyclocreatine protected against malonate-induced
  increases in the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic
  acid, biochemical markers of hydroxyl radical generation. Creatine
  administration protected against 3-NP-induced increases in 3-nitrotyrosine
  concentrations, a marker of peroxynitrite-mediated oxidative injury. Oral
  supplementation with creatine or cyclocreatine results in
  neuroprotective effects in vivo, which may
  represent a novel therapeutic strategy for HD and other neurodegenerative
  diseases.

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