Molecular Insights into NR4A2(Nurr1): an Emerging Target for Neuroprotective Therapy Against Neuroinflammation and Neuronal Cell Death

  • Md. Jakaria
  • Md. Ezazul Haque
  • Duk-Yeon Cho
  • Shofiul Azam
  • In-Su Kim
  • Dong-Kug ChoiEmail author


NR4A2 is a nuclear receptor and a transcription factor, with distinctive physiological features. In the cell nuclei of the central nervous system, it is widely expressed and identified as a crucial regulator of dopaminergic (DA) neuronal differentiation, survival, and maintenance. Importantly, it has regulated different genes crucial for dopaminergic signals, and its expression has been diminished in both aged and PD post-mortem brains and reduced in PD patients. In microglia and astrocytes, the expression of NR4A2 has been found where it can be capable of inhibiting the expression of proinflammatory mediators; hence, it protected inflammation-mediated DA neuronal death. In addition, NR4A2 plays neuroprotective role via regulating different signals. However, NR4A2 has been mainly focused on Parkinson’s research, but, in recent times, it has been studied in Alzheimer’s disease (AD), multiple sclerosis (MS), and stroke. Altered expression of NR4A2 is connected to AD progression, and activation of its may improve cognitive function. It is downregulated in peripheral blood mononuclear cells of MS patients; nonetheless, its role in MS has not been fully clear. miR-145-5p known as a putative regulator of NR4A2 and in a middle cerebral artery occlusion/reperfusion model, anti-miR-145-5p administration promoted neurological outcomes in rat. To date, various activators and modulators of NR4A2 have been discovered and investigated as probable therapeutic drugs in neuroinflammatory and neuronal cell death models. The NR4A2 gene and cell-based therapy are described as promising drug candidates for neurodegenerative diseases. Moreover, microRNA might have a crucial role in neurodegeneration via affecting NR4A2 expression. Herein, we present the role of NR4A2 in neuroinflammation and neuronal cell death focusing on neurodegenerative conditions and display NR4A2 as a promising therapeutic target for the therapy of neuroprotection.


NR4A2 Nuclear receptor Therapeutic target Neuroinflammation Neuronal cell death and neuroprotection 



6-hydroxyl dopamine


L-amino acid decarboxylase


Alzheimer’s disease


Activation function


C-terminal domain


cAMP response element-binding protein




Dopamine transporter


DNA binding domain


Delta-like non-canonical notch ligand 1


Glial cell line-derived neurotrophic factor




Interleukin 1-beta


Keyhole limpet hemocyanin1


Ligand-binding domain


Multiple sclerosis


N-terminal domain


Neurodegenerative diseases


Nuclear factor-kappaB


Nerve growth factor IB


Nuclear receptor subfamily 4 group A member 1


Nuclear receptor subfamily 4 group A member 2


Nuclear receptor subfamily 4 group A member 1


Neural stem cells


Olfactory ensheathing cells


Parkinson’s disease


Receptor-type tyrosine-protein phosphatase PCP-2


Retinoid X receptor


Substantia nigra


Tyrosine hydroxylase


Tumor necrosis factor-alpha

topo IIβ

DNA topoisomerase IIβ


Vasoactive intestinal peptide


Vesicular monoamine transporter-2


Availability of Data and Material

Not applicable.

Authors’ Contributions

MJ, I-SK, and D-KC conceived and designed the study. MJ performed the literature review, wrote the manuscript, and compiled the table. MJ and I-SK also produced the figures, and MEH, SA, and D-YC performed the literature review and data arrangement. D-KC also supervised and handled the correspondence. All authors read and approved the final manuscript.


This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (NRF-2017R1A2A2A07001035).

Compliance with Ethical Standards

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

Not applicable.

Consent for Publication

Not applicable.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Applied Life Sciences and Integrated Bioscience, Graduate SchoolKonkuk UniversityChungjuSouth Korea
  2. 2.Department of Integrated Bioscience and Biotechnology, College of Biomedical and Health Sciences and Research Institute of Inflammatory Diseases (RID)Konkuk UniversityChungjuSouth Korea

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