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Biochemistry of postmortem brains in Parkinson’s disease: historical overview and future prospects

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Neuropsychiatric Disorders An Integrative Approach

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURALTRANS,volume 72))

Abstract

Biochemical studies on postmortem brains of patients with Parkinson’s disease (PD) have greatly contributed to our understanding of the molecular pathogenesis of this disease. The discovery by 1960 of a dopamine deficiency in the nigro-striatal dopamine region of the PD brain was a landmark in research on PD. At that time we collaborated with Hirotaro Narabayashi and his colleagues in Japan and with Peter Riederer in Germany on the biochemistry of PD by using postmortem brain samples in their brain banks. We found that the activity, mRNA level, and protein content of tyrosine hydroxylase (TH), as well as the levels of the tetrahydrobiopterin (BH4) cofactor of TH and the activity of the BH4-synthesizing enzyme, GTP cyclohydrolase I (GCH1), were markedly decreased in the substantia nigra and striatum in the PD brain. In contrast, the molecular activity (enzyme activity/enzyme protein) of TH was increased, suggesting a compensatory increase in the enzyme activity. The mRNA levels of all four isoforms of human TH (hTHl-hTH4), produced by alternative mRNA splicing, were also markedly decreased. This finding is in contrast to a completely parallel decrease in the activity and protein content of dopamine β-hydroxylase (DBH) without changes in its molecular activity in cerebrospinal fluid (CSF) in PD. We also found that the activities and/or the levels of the mRNA and protein of aromatic L-amino acid decarboxylase (AADC, DOPA decarboxylase), DBH, phenylethanolamine N-methyltransferase (PNMT), which synthesize dopamine, noradrenaline, and adrenaline, respectively, were also decreased in PD brains, indicating that all catecholamine systems were widely impaired in PD brains.

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Authors and Affiliations

  1. Department of Brain Life Science, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, Japan

    Prof. Dr. T. Nagatsu

  2. Department of Pharmacology, School of Medicine,, Fujita Health University, Toyoake, Aichi, Japan

    Prof. Dr. T. Nagatsu & M. Sawada

Authors
  1. Prof. Dr. T. Nagatsu
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  2. M. Sawada
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Correspondence to T. Nagatsu .

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Editors and Affiliations

  1. Klinik und Poliklinik für Kinder- und Jugendpsychiatrie und Psychotherapie, Würzburg, Germany

    M. Gerlach

  2. Klinik und Poliklinik für Psychiatrie und Psychotherapie, Würzburg, Germany

    Jürgen Deckert

  3. Prince of Wales Medical Research Institute, Sydney, Australia

    K. Double

  4. Institut für Virologie und Immunobiologie, Würzburg, Germany

    E. Koutsilieri

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Nagatsu, T., Sawada, M. (2007). Biochemistry of postmortem brains in Parkinson’s disease: historical overview and future prospects. In: Gerlach, M., Deckert, J., Double, K., Koutsilieri, E. (eds) Neuropsychiatric Disorders An Integrative Approach. Journal of Neural Transmission. Supplementa, vol 72. Springer, Vienna. https://doi.org/10.1007/978-3-211-73574-9_14

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  • DOI: https://doi.org/10.1007/978-3-211-73574-9_14

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