TY - JOUR
T1 - Want of Wnt in Parkinson's disease
T2 - Could sFRP disrupt interplay between Nurr1 and Wnt signaling?
AU - Gamit, Naisarg
AU - Dharmarajan, Arun
AU - Sethi, Gautam
AU - Warrier, Sudha
N1 - Funding Information:
NG is thankful for the TMA Pai scholarship from Manipal Academy of Higher Education (MAHE), India. This work was supported by the Science and Engineering Research Board, Department of Science and Technology, India [SPG/2021/003724] and the Department of Health Research, Ministry of Health and Family Welfare, India [R.11013/27/2021-GIA/HR] awarded to SW.
Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/6
Y1 - 2023/6
N2 - Nuclear receptor related 1 (Nurr1) is a transcription factor known to regulate the development and maintenance of midbrain dopaminergic (mDA) neurons. Reports have confirmed that defect or obliteration of Nurr1 results in neurodegeneration and motor function impairment leading to Parkinson's disease (PD). Studies have also indicated that Nurr1 regulates the expression of alpha-synuclein (α-SYN) and mutations in Nurr1 cause α-SYN overexpression, thereby increasing the risk of PD. Nurr1 is modulated via various pathways including Wnt signaling pathway which is known to play an important role in neurogenesis, and deregulation of it contributes to PD pathogenesis. Both Wnt/β-catenin dependent and independent pathways are implicated in the activation of Nurr1 and subsequent downregulation of α-SYN. This review highlights the interaction between Nurr1 and Wnt signaling pathways in mDA neuronal development. We further hypothesize how modulation of Wnt signaling pathway by its antagonist, secreted frizzled related proteins (sFRPs) could be a potential route to treat PD.
AB - Nuclear receptor related 1 (Nurr1) is a transcription factor known to regulate the development and maintenance of midbrain dopaminergic (mDA) neurons. Reports have confirmed that defect or obliteration of Nurr1 results in neurodegeneration and motor function impairment leading to Parkinson's disease (PD). Studies have also indicated that Nurr1 regulates the expression of alpha-synuclein (α-SYN) and mutations in Nurr1 cause α-SYN overexpression, thereby increasing the risk of PD. Nurr1 is modulated via various pathways including Wnt signaling pathway which is known to play an important role in neurogenesis, and deregulation of it contributes to PD pathogenesis. Both Wnt/β-catenin dependent and independent pathways are implicated in the activation of Nurr1 and subsequent downregulation of α-SYN. This review highlights the interaction between Nurr1 and Wnt signaling pathways in mDA neuronal development. We further hypothesize how modulation of Wnt signaling pathway by its antagonist, secreted frizzled related proteins (sFRPs) could be a potential route to treat PD.
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U2 - 10.1016/j.bcp.2023.115566
DO - 10.1016/j.bcp.2023.115566
M3 - Review article
C2 - 37088155
AN - SCOPUS:85153587775
SN - 0006-2952
VL - 212
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
M1 - 115566
ER -