Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5<scp>XFAD</scp>mice, an animal model of Alzheimer's disease

Moon, Minho; Jeong, Inhye; Kim, Chun Hyung; Kim, Jihong; Lee, Paula K.J.; Mook‐Jung, Inhee; Leblanc, Pierre; Kim, Kwang S.

doi:10.1111/jnc.12935

Cited by 39 publications

(51 citation statements)

References 30 publications

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“…In the present study, Nurr1 immunoreactivity was primarily observed in pyramidal neurons and granule cells, which are well established as principal neurons of the hippocampus ( 28 ), in young, adult and aged gerbil hippocampi. The results of Nurr1 immunoreactivity in the hippocampi were generally consistent with those of a previous study in C57BL/6 mice, which demonstrated that clear and specific Nurr1 immunoreactivity occurred in the hippocampus ( 29 ).…”

Section: Discussionsupporting

confidence: 91%

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

et al. 2018

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Nuclear receptor related-1 protein (Nurr1) serves important roles in hippocampal-dependent cognitive process. In the present study, the protein expression of Nurr1 was compared in the hippocampi of young [postnatal month 3 (PM 3)], adult (PM 12) and aged (PM 24) gerbils using western blot analysis and immunohistochemistry. Results indicated that the protein level of Nurr1 was significantly and gradually decreased in the gerbil hippocampus with increasing age. In addition, strong Nurr1 immunoreactivity was primarily observed in pyramidal neurons and granule cells of the hippocampus in the young group, which was determined to be reduced in the adult group and to a greater extent in the aged group. Collectively the data demonstrated that Nurr1 immunoreactivity was gradually and markedly decreased during normal aging. These results indicate that gradual decrease of Nurr1 expression in the hippocampus may be associated with the normal aging process and a decline in hippocampus-dependent cognitive function.

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Section: Discussionsupporting

confidence: 91%

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

et al. 2018

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“…It is expressed in several brain areas and plays important roles in various neural processes including cognitive functions and/or long-term memory in forebrain areas and hippocampal formation. Immune-fluorescence staining with a specific NR4A2 antibody in 5XFAD mice showed that the NR4A2 protein was prominently localized in brain areas with Aβ plaque accumulation, highlighting a possible involvement of this protein in AD pathology 60 . The potential regulation of NR4A2 by miR-184 requires further functional testing but leads us to suggest that the loss of expression of miR-184 in LOAD hippocampus may contribute to NR4A2 accumulation in Aβ plaques.…”

Section: Discussionmentioning

confidence: 96%

Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease

Annese

Manzari

Lionetti

et al. 2018

Sci Rep

107

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Alzheimer’s Disease (AD) is the most common cause of dementia affecting the elderly population worldwide. We have performed a comprehensive transcriptome profiling of Late-Onset AD (LOAD) patients using second generation sequencing technologies, identifying 2,064 genes, 47 lncRNAs and 4 miRNAs whose expression is specifically deregulated in the hippocampal region of LOAD patients. Moreover, analyzing the hippocampal, temporal and frontal regions from the same LOAD patients, we identify specific sets of deregulated miRNAs for each region, and we confirm that the miR-132/212 cluster is deregulated in each of these regions in LOAD patients, consistent with these miRNAs playing a role in AD pathogenesis. Notably, a luciferase assay indicates that miR-184 is able to target the 3’UTR NR4A2 - which is known to be involved in cognitive functions and long-term memory and whose expression levels are inversely correlated with those of miR-184 in the hippocampus. Finally, RNA editing analysis reveals a general RNA editing decrease in LOAD hippocampus, with 14 recoding sites significantly and differentially edited in 11 genes. Our data underline specific transcriptional changes in LOAD brain and provide an important source of information for understanding the molecular changes characterizing LOAD progression.

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“…A reduction in Nurr1 levels has been reported in several neurodegenerative diseases [18]. The importance of Nurr1 in PD pathology is well established [19], and reduced Nurr1 levels have been reported in AD animal models and the brains of patients with AD [112,113]. Therefore, Nurr1 has been suggested as a valid biomarker for neurodegenerative diseases and a therapeutic target [18,23].…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Stimulation of Nurr1 Promotes Cell Cycle Progression in Adult Hippocampal Neural Stem Cells

Moon

Jeon

Kim

et al. 2019

IJMS

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Nuclear receptor related-1 (Nurr1) protein performs a crucial role in hippocampal neural stem cell (hNSC) development as well as cognitive functions. We previously demonstrated that the pharmacological stimulation of Nurr1 by amodiaquine (AQ) promotes spatial memory by enhancing adult hippocampal neurogenesis. However, the role of Nurr1 in the cell cycle regulation of the adult hippocampus has not been investigated. This study aimed to examine changes in the cell cycle-related molecules involved in adult hippocampal neurogenesis induced by Nurr1 pharmacological stimulation. Fluorescence-activated cell sorting (FACS) analysis showed that AQ improved the progression of cell cycle from G0/G1 to S phase in a dose-dependent manner, and MEK1 or PI3K inhibitors attenuated this progression. In addition, AQ treatment increased the expression of cell proliferation markers MCM5 and PCNA, and transcription factor E2F1. Furthermore, pharmacological stimulation of Nurr1 by AQ increased the expression levels of positive cell cycle regulators such as cyclin A and cyclin-dependent kinases (CDK) 2. In contrast, levels of CDK inhibitors p27KIP1 and p57KIP2 were reduced upon treatment with AQ. Similar to the in vitro results, RT-qPCR analysis of AQ-administered mice brains revealed an increase in the levels of markers of cell cycle progression, PCNA, MCM5, and Cdc25a. Finally, AQ administration resulted in decreased p27KIP1 and increased CDK2 levels in the dentate gyrus of the mouse hippocampus, as quantified immunohistochemically. Our results demonstrate that the pharmacological stimulation of Nurr1 in adult hNSCs by AQ promotes the cell cycle by modulating cell cycle-related molecules.

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Correlation between orphan nuclear receptor Nurr1 expression and amyloid deposition in 5XFADmice, an animal model of Alzheimer's disease

Cited by 39 publications

References 30 publications

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

Age‑dependent decrease of Nurr1 protein expression in the gerbil hippocampus

Whole transcriptome profiling of Late-Onset Alzheimer’s Disease patients provides insights into the molecular changes involved in the disease

Pharmacological Stimulation of Nurr1 Promotes Cell Cycle Progression in Adult Hippocampal Neural Stem Cells

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