TY - JOUR
T1 - The Crucial Roles of Pitx3 in Midbrain Dopaminergic Neuron Development and Parkinson’s Disease-Associated Neurodegeneration
AU - Wang, Xin
AU - Chen, Xi
AU - Liu, Guangdong
AU - Cai, Huaibin
AU - Le, Weidong
N1 - Funding Information:
This work was supported in part by funding from the National Natural Science Foundation of China (Key Program) (32220103006), the Key Research and Development Program of Sichuan (2021YFS0382), the National Natural Science Foundation of China (General Program) (82271524), and the intramural program of National Institute on Aging, USA (ZIA AG000944, AG000928).
Publisher Copyright:
© 2023 by the authors.
PY - 2023/5/11
Y1 - 2023/5/11
N2 - 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.
AB - 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.
KW - Parkinson’s disease
KW - midbrain dopaminergic neuron development
KW - paired-like homeodomain transcription factor 3 (Pitx3)
KW - transcription factors
KW - Animals
KW - Dopamine
KW - Homeodomain Proteins/genetics
KW - Mice
KW - Dopaminergic Neurons/metabolism
KW - Transcription Factors/genetics
KW - Mesencephalon/metabolism
KW - Parkinson Disease/genetics
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U2 - 10.3390/ijms24108614
DO - 10.3390/ijms24108614
M3 - Review article
C2 - 37239960
AN - SCOPUS:85160373400
SN - 1661-6596
VL - 24
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 10
M1 - 8614
ER -