The Crucial Roles of Pitx3 in Midbrain Dopaminergic Neuron Development and Parkinson’s Disease-Associated Neurodegeneration

Xin Wang, Xi Chen, Guangdong Liu, Huaibin Cai, Weidong Le

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

The degeneration of midbrain dopaminergic (mDA) neurons, particularly in the substantia nigra pars compacta (SNc), is one of the most prominent pathological hallmarks of Parkinson’s disease (PD). To uncover the pathogenic mechanisms of mDA neuronal death during PD may provide therapeutic targets to prevent mDA neuronal loss and slow down the disease’s progression. Paired-like homeodomain transcription factor 3 (Pitx3) is selectively expressed in the mDA neurons as early as embryonic day 11.5 and plays a critical role in mDA neuron terminal differentiation and subset specification. Moreover, Pitx3-deficient mice exhibit some canonical PD-related features, including the profound loss of SNc mDA neurons, a dramatic decrease in striatal dopamine (DA) levels, and motor abnormalities. However, the precise role of Pitx3 in progressive PD and how this gene contributes to mDA neuronal specification during early stages remains unclear. In this review, we updated the latest findings on Pitx3 by summarizing the crosstalk between Pitx3 and its associated transcription factors in mDA neuron development. We further explored the potential benefits of Pitx3 as a therapeutic target for PD in the future. To better understand the transcriptional network of Pitx3 in mDA neuron development may provide insights into Pitx3-related clinical drug-targeting research and therapeutic approaches.

Original languageEnglish (US)
Article number8614
JournalInternational journal of molecular sciences
Volume24
Issue number10
DOIs
StatePublished - May 11 2023

Keywords

  • Parkinson’s disease
  • midbrain dopaminergic neuron development
  • paired-like homeodomain transcription factor 3 (Pitx3)
  • transcription factors
  • Animals
  • Dopamine
  • Homeodomain Proteins/genetics
  • Mice
  • Dopaminergic Neurons/metabolism
  • Transcription Factors/genetics
  • Mesencephalon/metabolism
  • Parkinson Disease/genetics

ASJC Scopus subject areas

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

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