The role of NURR1 in metabolic abnormalities of Parkinson’s disease

Al‐Nusaif, Murad; Yang, Yuting; Li, Song; Cheng, Cheng

doi:10.1186/s13024-022-00544-w

Cited by 28 publications

(15 citation statements)

References 246 publications

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“…A strong activation of microglia (Mic) is observed in the brain of PD patients, which is not a widespread inflammatory response but has specific pathological outcomes in specific areas, which is closely related to the death of dopaminergic (DA) neurons in the SN . The activation of microglia plays a more important role in the pathogenesis and progression of PD . Interestingly, here, we identified that a natural compound derived from plantain seeds, PMS, could alleviate SN damage in PD mice by reducing microglia polarization .…”

Section: Discussionmentioning

confidence: 84%

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Guo

Chen

2023

ACS Chem. Neurosci.

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Parkinson’s disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.

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Section: Discussionmentioning

confidence: 84%

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Guo

Chen

2023

ACS Chem. Neurosci.

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“…Nuclear receptor subfamily 4 group A, or simply NR4A, proteins for instance are nuclear receptor (NR) transcription factors that play a regulatory role in neuronal development, in ammation, and memory formation 28 . The associated disorders are related to dopaminergic dysfunction, including PD, schizophrenia, and manic depression 29,30 . GADD45B, on the other hand, is a neuronal activity sensor induced by neuronal stress and essential for adult neurogenesis 31 .…”

Section: Discussionmentioning

confidence: 99%

Impaired ATF3 Signaling Involves SNAP25 in SOD1 Mutant ALS Patients

Yazar

Kühlwein

Knehr

et al. 2023

Preprint

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Epigenetic remodeling is emerging as a critical process for several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). Genetics alone fails to explain the etiology of ALS, the investigation of the epigenome might therefore provide novel insights into the molecular mechanisms of the disease. In this study, we interrogated the epigenetic landscape in peripheral blood mononuclear cells (PBMCs) of familial ALS (fALS) patients with either chromosome 9 open reading frame 72 (C9orf72) or superoxide dismutase 1 (SOD1) mutation and aimed to identify key epigenetic footprints of the disease. To this end, we used an integrative approach that combines chromatin immunoprecipitation targeting H3K27me3 (ChIP-Seq) with the matching gene expression data to gain new insights into the likely impact of blood-specific chromatin remodeling on ALS-related molecular mechanisms. We demonstrated that one of the hub molecules that modulates changes in PBMC transcriptome in SOD1-mutant ALS patients is ATF3, which has been previously reported in an SOD1G93A mouse model. We also identified potential suppression of SNAP25, with impaired ATF3 signaling in SOD1-mutant ALS blood. Together, our study shed light on the mechanistic underpinnings of SOD1 mutations in ALS.

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“…Nurr1, a transcription factor of the NR4A subgroup of nuclear receptor superfamily, plays key roles in the development and maintenance of DA neurons 20 , 22 , 53 . Nurr1 deletion in adult DA neurons gives rise to behavioral impairments, DA deficits including decreased TH, DAT and VMAT2 in the striatum, and loss of DA fibers in the midbrain and striatum 23 , 54 .…”

Section: Discussionmentioning

confidence: 99%

Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice

Skiteva

Yao

Mantas

et al. 2023

npj Parkinsons Dis.

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In Parkinson’s disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies. Calcium influx during pacemaker firing might contribute to neuronal loss, but it is not known if dysfunctions of voltage-gated calcium channels (VGCCs) occur in DA neurons somata and axon terminals. We investigated T-type and L-type VGCCs in SNc-DA neurons of two mouse models of PD: mice with a deletion of the Nurr1 gene in DA neurons from an adult age (cNurr1 mice), and mice bearing the G2019S mutation in the gene coding for LRRK2 (G2019S mice). Adult cNurr1 mice displayed motor and DA deficits, while middle-aged G2019S mice did not. The number and morphology of SNc-DA neurons, most of their intrinsic membrane properties and pacemaker firing were unaltered in cNurr1 and G2019S mice compared to their control and wild-type littermates. L-type VGCCs contributed to the pacemaker firing of SNc-DA neurons in G2019S mice, but not in control, wild-type, and cNurr1 mice. In cNurr1 mice, but not G2019S mice, the contribution of T-type VGCCs to the pacemaker firing of SNc-DA neurons was reduced, and somatic dopamine-D2 autoreceptors desensitized more. Altered contribution of L-type and T-type VGCCs to the pacemaker firing was not observed in the presence of a LRRK2 kinase inhibitor in G2019S mice, and in the presence of a flavonoid with antioxidant activity in G2019S and cNurr1 mice. The role of L-type and T-type VGCCs in controlling dopamine release from axon terminals in the striatum was unaltered in cNurr1 and G2019S mice. Our findings uncover opposite changes, linked to oxidative stress, in the function of two VGCCs in DA neurons somata, but not axon terminals, in two different experimental PD models.

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The role of NURR1 in metabolic abnormalities of Parkinson’s disease

Cited by 28 publications

References 246 publications

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Plantamajoside Alleviates Substantia Nigra Damage in Parkinson’s Disease Mice by Inhibiting HDAC2/MAPK Signaling and Reducing Microglia Polarization

Impaired ATF3 Signaling Involves SNAP25 in SOD1 Mutant ALS Patients

Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice

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