N-propanoylmannosamine interferes with O-GlcNAc modification of the tyrosine 3-monooxygenase and stimulates dopamine secretion

Kaya Bork, Christoph Kannicht, Sabine Nöhring, Werner Reutter, Wenke Weidemann, Gerald Warren Hart, Rüdiger Horstkorte

Research output: Contribution to journalArticlepeer-review

Abstract

The most consistent neurochemical abnormality in Parkinson's disease is degeneration of dopaminergic neurons in the substantia nigra, leading to a reduction of striatal dopamine levels. The rate-limiting step in the biosynthesis of dopamine, noradrenalin, and adrenalin is catalyzed by tyrosine 3-monooxygenase (=tyrosine hydroxylase), which catalyzes the formation of L-DOPA. In earlier studies, we demonstrated that the novel synthetic sialic acid precursor N-propanoylmannosamine is a potent stimulator of axonal growth and promotes reestablishment of the perforant pathway from layer II of cortical neurons to the outer molecular layer of the dentate gyrus. Here we show that application of N-propanoylmannosamine leads to increased biosynthesis and secretion of dopamine. This increased biosynthesis of dopamine is due to decreased expression of O-linked N-acetylglucosamine on tyrosine 3-monooxygenase. Intracellular attachment of O-linked N-acetylglucosamine to serine and threonine residues hinders phosphorylation, thereby regulating the activity of the proteins concerned. We therefore propose a model in which the application of ManNProp leads to increased phosphorylation and activation of tyrosine 3-monooxygenase, which in turn leads to an increased synthesis of dopamine.

Original languageEnglish (US)
Pages (from-to)647-652
Number of pages6
JournalJournal of Neuroscience Research
Volume86
Issue number3
DOIs
StatePublished - Feb 15 2008

Keywords

  • Dopamine
  • Glycosylation
  • PC12 cells

ASJC Scopus subject areas

  • Neuroscience(all)

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