A Generalised Increase in Protein Carbonyls in the Brain in Parkinson's but Not Incidental Lewy Body Disease

Authors

  • Zafar I. Alam,

    1. Neurodegenerative Disease Research Centre, Pharmacology Group, King's College; and
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  • Susan E. Daniel,

    1. Parkinson's Disease Society Brain Research Centre, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, England
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  • Andrew J. Lees,

    1. Parkinson's Disease Society Brain Research Centre, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, England
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  • David C. Marsden,

    1. Parkinson's Disease Society Brain Research Centre, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, England
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  • Peter Jenner,

    1. Neurodegenerative Disease Research Centre, Pharmacology Group, King's College; and
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  • Barry Halliwell

    Corresponding author
    1. Neurodegenerative Disease Research Centre, Pharmacology Group, King's College; and
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Address correspondence and reprint requests to Prof. B. Halliwell at Pharmacology Group, King's College, Manresa Road, London, SW3 6LX, U.K.

Abstract

Abstract: The degeneration of neurones in Parkinson's disease (PD) may involve oxidative stress. Previously, increased lipid peroxidation and oxidative DNA damage have been reported in parkinsonian substantia nigra. In the present study the protein carbonyl assay was used to assess oxidative protein damage in postmortem brain tissue from patients with PD and age-matched controls. In brain areas associated with PD, such as substantia nigra, caudate nucleus, and putamen, there was a significant increase in carbonyl levels. However, increased carbonyl levels were also found in areas of the brain not thought to be affected in PD. This perhaps suggests that protein carbonyl formation is related to therapy with l-DOPA, which can exert prooxidant properties in vitro. Consistent with this possibility, brain regions from individuals with incidental Lewy body disease (putative presymptomatic PD) showed no rise in carbonyls in any brain areas. Our data show that either oxidative protein damage occurs widely but late in PD brain, and/or that l-DOPA treatment contributes to protein oxidation.

Abbreviations used: HNE, 4-hydroxy-2-nonenal; ILBD, incidental Lewy body disease; PD, Parkinson's disease; PMI, postmortem interval.

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