Want of Wnt in Parkinson's disease: Could sFRP disrupt interplay between Nurr1 and Wnt signaling?

Naisarg Gamit; Arun Dharmarajan; Gautam Sethi; Sudha Warrier

doi:10.1016/j.bcp.2023.115566

Want of Wnt in Parkinson's disease: Could sFRP disrupt interplay between Nurr1 and Wnt signaling?

Biochem Pharmacol. 2023 Jun:212:115566. doi: 10.1016/j.bcp.2023.115566. Epub 2023 Apr 22.

Authors

Naisarg Gamit¹, Arun Dharmarajan², Gautam Sethi³, Sudha Warrier⁴

Affiliations

¹ Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore 560 065, India.
² Department of Biomedical Sciences, Faculty of Biomedical Sciences, Technology and Research, Sri Ramachandra Institute of Higher Education and Research, Chennai 600 116, India; School of Pharmacy and Biomedical Sciences, Curtin Medical School, Curtin University, Perth, Western Australia 6102, Australia; Curtin Health and Innovation Research Institute, Curtin University, Perth, Western Australia 6102, Australia; School of Human Sciences, Faculty of Life and Physical Sciences, The University of Western Australia, Perth, Western Australia 6009, Australia.
³ Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117 600, Singapore.
⁴ Division of Cancer Stem Cells and Cardiovascular Regeneration, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore 560 065, India; Cuor Stem Cellutions Pvt Ltd, Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education (MAHE), Bangalore 560 065, India. Electronic address: sudha.warrier@manipal.edu.

PMID: 37088155
DOI: 10.1016/j.bcp.2023.115566

Abstract

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.

Keywords: Alpha-synuclein; Nurr1; Parkinson’s disease; Wnt antagonist; Wnt signaling; sFRP.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Dopaminergic Neurons / metabolism
Humans
Parkinson Disease* / genetics
Parkinson Disease* / metabolism
Receptors, Cytoplasmic and Nuclear / metabolism
Transcription Factors / metabolism
Wnt Signaling Pathway / physiology

Substances

Transcription Factors
Receptors, Cytoplasmic and Nuclear