Degradation of tyrosine hydroxylase by the ubiquitin-proteasome system in the pathogenesis of Parkinson’s disease and dopa-responsive dystonia

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3 Citations (Scopus)

Abstract

Nigrostriatal dopaminergic systems govern physiological functions related to locomotion, and their dysfunction leads to movement disorders, such as Parkinson’s disease and dopa-responsive dystonia (Segawa disease). Previous studies revealed that expression of the gene encoding nigrostriatal tyrosine hydroxylase (TH), a rate-limiting enzyme of dopamine biosynthesis, is reduced in Parkinson’s disease and dopa-responsive dystonia; however, the mechanism of TH depletion in these disorders remains unclear. In this article, we review the molecular mechanism underlying the neurodegeneration process in dopamine-containing neurons and focus on the novel degradation pathway of TH through the ubiquitin-proteasome system to advance our understanding of the etiology of Parkinson’s disease and dopa-responsive dystonia. We also introduce the relation of α-synuclein propagation with the loss of TH protein in Parkinson’s disease as well as anticipate therapeutic targets and early diagnosis of these diseases.

Original languageEnglish
Article number3779
JournalInternational journal of molecular sciences
Volume21
Issue number11
DOIs
Publication statusPublished - 2020 Jun 1

Keywords

  • Dopa-responsive dystonia
  • Fatty acid-binding protein 3
  • Parkinson’s disease
  • Proteasomal degradation
  • Tyrosine hydroxylase
  • Ubiquitin-proteasome system
  • Ubiquitination
  • α-synuclein

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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