General Information:

Id: 1,124
Diseases: Parkinson disease
Mammalia
BTO:0000078 microglia; BTO:0000099 astrocyte; BTO:0003350 BV-2 cell
article
Reference: Saijo K et al.(2009) A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death Cell 137: 47-59 [PMID: 19345186]

Interaction Information:

Comment Analysis of Nurr1 protein and mRNA levels in primary human and mouse microglia, primary human astrocytes, and the BV2 microglia cell line demonstrated significant protein expression under basal conditions and induction of Nurr1 mRNA in microglia in response to LPS.
Formal Description
Interaction-ID: 7222

drug/chemical compound

Lipopolysaccharide

increases_expression of

gene/protein

NR4A2

in microglia and astrocytes
Comment Analysis of Nurr1 protein and mRNA levels in primary human and mouse microglia, primary human astrocytes, and the BV2 microglia cell line demonstrated significant protein expression under basal conditions and induction of Nurr1 mRNA in microglia in response to LPS.
Formal Description
Interaction-ID: 7223

drug/chemical compound

Lipopolysaccharide

increases_quantity of

gene/protein

NR4A2

in microglia and astrocytes
Comment Nurr1 protects TH+ neurons from LPS-induced inflammation in vivo. LPS injection was associated with detection of caspase-3 cleavage, suggesting that loss of TH+ cells was due to cell death rather than to loss of TH expression.
Formal Description
Interaction-ID: 7225

drug/chemical compound

Lipopolysaccharide

increases_activity of

process

neuron death

in substantia nigra
Comment Nurr1 protects TH+ neurons from LPS-induced inflammation in vivo. LPS injection was associated with detection of caspase-3 cleavage, suggesting that loss of TH+ cells was due to cell death rather than to loss of TH expression.
Formal Description
Interaction-ID: 7227

gene/protein

NR4A2

decreases_activity of

process

neuron death

in substantia nigra; induced by addition of LPS
Comment Nurr1 protects TH+ neurons from LPS-induced inflammation in vivo. LPS injection was associated with detection of caspase-3 cleavage, suggesting that loss of TH+ cells was due to cell death rather than to loss of TH expression.
Formal Description
Interaction-ID: 7228

gene/protein

NR4A2

decreases_activity of

drug/chemical compound

Lipopolysaccharide

in substantia nigra
Comment Nurr1 protects TH+ neurons from LPS-induced inflammation in vivo. LPS injection was associated with detection of caspase-3 cleavage, suggesting that loss of TH+ cells was due to cell death rather than to loss of TH expression.
Formal Description
Interaction-ID: 7232

drug/chemical compound

Lipopolysaccharide

increases_activity of

gene/protein

CASP3

in substantia nigra
Drugbank entries Show/Hide entries for CASP3
Comment Reduction of Nurr1 expression in the SN also resulted in exaggerated expression of inflammatory mediators in response to LPS injection, including iNOS, TNFalpha and IL1beta.
Formal Description
Interaction-ID: 7233

drug/chemical compound

Lipopolysaccharide

increases_quantity of

gene/protein

NOS2

in substantia nigra
Drugbank entries Show/Hide entries for NOS2
Comment Reduction of Nurr1 expression in the SN also resulted in exaggerated expression of inflammatory mediators in response to LPS injection, including iNOS, TNFalpha and IL1beta.
Formal Description
Interaction-ID: 7234

drug/chemical compound

Lipopolysaccharide

increases_quantity of

gene/protein

TNF

in substantia nigra
Drugbank entries Show/Hide entries for TNF
Comment Reduction of Nurr1 expression in the SN also resulted in exaggerated expression of inflammatory mediators in response to LPS injection, including iNOS, TNFalpha and IL1beta.
Formal Description
Interaction-ID: 7235

drug/chemical compound

Lipopolysaccharide

increases_quantity of

gene/protein

IL1B

in substantia nigra
Drugbank entries Show/Hide entries for IL1B
Comment A30P expression alone caused weak inflammation in the SN, whereas reduction of Nurr1 expression in the context of A30P expression resulted in a dramatic increase, indicating that Nurr1 limits inflammatory responses in the CNS.
Formal Description
Interaction-ID: 7236

gene/protein mutant

SNCA-p.A30P

increases_activity of

in substantia nigra
Comment A30P expression alone caused weak inflammation in the SN, whereas reduction of Nurr1 expression in the context of A30P expression resulted in a dramatic increase, indicating that Nurr1 limits inflammatory responses in the CNS.
Formal Description
Interaction-ID: 7237

gene/protein

NR4A2

decreases_activity of

in substantia nigra; via recruiting the CoREST-CtBP complex
Comment Microglia are the initial responders to LPS-mediated inflammation and that astrocytes amplify the production of neurotoxic factors after the microglial activation.
Formal Description
Interaction-ID: 7246

drug/chemical compound

Lipopolysaccharide

increases_activity of

primarily in microglia cells
Comment Chromatin immunoprecipitation experiments indicated that Nurr1 was recruited to LPS-responsive promoters following LPS treatment, exemplified by the TNFalpha promoter, suggesting that it was acting locally to repress transcription.
Formal Description
Interaction-ID: 7247

gene/protein

NR4A2

decreases_expression of

gene/protein

TNF

by interacting with TNFalpha promoter region following LPS treatment
Drugbank entries Show/Hide entries for TNF
Comment Nurr1 was able to repress iNOS induction by LPS.
Formal Description
Interaction-ID: 7248

gene/protein

NR4A2

decreases_expression of

gene/protein

NOS2

following LPS treatment and by recruiting the CoREST-CtBP complex
Drugbank entries Show/Hide entries for NOS2
Comment Nurr1 could be SUMOylated with SUMO2 and SUMO3 using PIAS4 as an E3 ligase.
Formal Description
Interaction-ID: 7250

gene/protein

PIAS4

increases_ubiquitination/sumoylation of

gene/protein

NR4A2

at Lys-558 and, to a lesser extent Lys-576
Comment IL1beta stimulation could induce SUMOylation of Nurr1 in the absence of overexpression of PIAS4.
Formal Description
Interaction-ID: 7251

gene/protein

IL1B

increases_ubiquitination/sumoylation of

gene/protein

NR4A2

if NURR1 is ubiquitinated by PIAS4
Drugbank entries Show/Hide entries for IL1B
Comment Nurr1 interacts with NF-kappaB-p65, a transcription factor involved in inflammation. The interaction was significantly enhanced by LPS treatment.
Formal Description
Interaction-ID: 7252

gene/protein

NR4A2

interacts (colocalizes) with

gene/protein

RELA

if p65 has been phosphorylated by GSK3beta at Ser-468
Drugbank entries Show/Hide entries for RELA
Comment Nurr1 interacts with NF-kappaB-p65, a transcription factor involved in inflammation. The interaction was significantly enhanced by LPS treatment.
Formal Description
Interaction-ID: 7253

gene/protein

RELA

affects_activity of

via NF-kappaB signaling
Drugbank entries Show/Hide entries for RELA
Comment GSK3beta phosphorylates NF-kappaB-p65 at serine-468, which is associated with negative regulation of NF-kappaB signaling.
Formal Description
Interaction-ID: 7254

gene/protein

GSK3B

increases_phosphorylation of

gene/protein

RELA

at Ser-468
Drugbank entries Show/Hide entries for GSK3B or RELA
Comment NURR1 interacts with CoREST thus recruiting CoREST complex to target genes.
Formal Description
Interaction-ID: 7256

gene/protein

NR4A2

interacts (colocalizes) with

gene/protein

RCOR1

Comment Nurr1 functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes.
Formal Description
Interaction-ID: 8760

gene/protein

NR4A2

decreases_activity of

Comment Nurr1 functions to inhibit expression of pro-inflammatory neurotoxic mediators in both microglia and astrocytes.
Formal Description
Interaction-ID: 8761

gene/protein

NR4A2

decreases_activity of