The pathological roles of NDRG2 in Alzheimer's disease, a study using animal models and APPwt‐overexpressed cells

Rong, Xianfang; Sun, Yingni; Li, Dongmei; Yin, Huajing; Peng, Ying; Xu, Shixiao; Wang, Xiaoliang

doi:10.1111/cns.12716

Cited by 27 publications

(25 citation statements)

References 34 publications

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“…might play a role in generating Aβ [44]. Collectively, the 15 genes are not significantly enriched to be involved with any biological pathway; however, individually, these genes may play an essential role in the pathological aspect of AD and may provide new therapeutic targets for disease intervention.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains

Patel

Curtis

Lee

et al. 2019

Preprint

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Individuals with intact cognition and neuropathology consistent with Alzheimer's disease (AD) are referred to as asymptomatic AD (AsymAD). These individuals are highly likely to develop AD, yet transcriptomic changes in the brain which might reveal mechanisms for their AD vulnerability are currently unknown. Entorhinal cortex, frontal cortex, temporal cortex and cerebellum tissue from 27 control, 33AsymAD and 52 AD human brains were microarray expression profiled. Differential expression analysis identified a significant increase of transcriptomic activity in the frontal cortex of AsymAD subjects, suggesting fundamental changes in AD may initially begin within the frontal cortex region prior to AD diagnosis. Co-expression analysis identified an overactivation of the brain "glutamate-glutamine cycle", and disturbances in the brain energy pathways in both AsymAD and AD subjects, while connectivity of key hub genes in this network indicates a shift from an already increased cell proliferation in AsymAD subjects to stress response and removal of amyloidogenic proteins in AD subjects. This study provides new insight into the earliest biological changes occurring in the brain prior to the manifestation of clinical AD symptoms and provides new potential therapeutic targets for early disease intervention.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains

Patel

Curtis

Lee

et al. 2019

Preprint

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“…So far, the deficiency of innate immune ability to clear Aβ deposits (rather than overproduction of them) has been widely accepted as one of the most important causes of AD pathogenesis, and current research was gradually moved from blocking the production of Aβ deposits to rebalancing the immune system of AD patients . For example, interleukin (IL)‐10, one of the best known inflammatory cytokines, was a major regulator of macrophages .…”

Section: Introductionmentioning

confidence: 99%

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

et al. 2018

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The well-reproducible results showed the good performance of the combinatorial approach, and the remaining five new targets could be a good starting point for our understanding of the pathogenesis and drug discovery of AD. Moreover, this study supported validity of the combinatorial approach integrating ontology inference with network analysis in the discovery of novel drug target for neurological diseases.

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“…NDRG2 may function in synapse formation, neural differentiation, and axon survival in response to glucocorticoids (Deng et al 2003;Nichols et al 2005). Prior studies confirmed the increase of NDRG2 levels in AD dystrophic neurons and senile plaques (Mitchelmore et al 2004) as well as APP/PS1 transgenic mice brains (Rong et al 2017). The SNO sites described in this study (amino acid position 255 and 274) have been previously identified in an experiment utilizing induced nitrosylation, but the functional consequences of these modifications are unknown (Kohr et al 2012).…”

Section: Discussionmentioning

confidence: 92%

Quantitative proteomics of synaptosome S‐nitrosylation in Alzheimer’s disease

Wijasa

Sylvester

Brocke‐Ahmadinejad

et al. 2019

Journal of Neurochemistry

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Increasing evidence suggests that both synaptic loss and neuroinflammation constitute early pathologic hallmarks of Alzheimer’s disease. A downstream event during inflammatory activation of microglia and astrocytes is the induction of nitric oxide synthase type 2, resulting in an increased release of nitric oxide and the post‐translational S‐nitrosylation of protein cysteine residues. Both early events, inflammation and synaptic dysfunction, could be connected if this excess nitrosylation occurs on synaptic proteins. In the long term, such changes could provide new insight into patho‐mechanisms as well as biomarker candidates from the early stages of disease progression. This study investigated S‐nitrosylation in synaptosomal proteins isolated from APP/PS1 model mice in comparison to wild type and NOS2−/− mice, as well as human control, mild cognitive impairment and Alzheimer’s disease brain tissues. Proteomics data were obtained using an established protocol utilizing an isobaric mass tag method, followed by nanocapillary high performance liquid chromatography tandem mass spectrometry. Statistical analysis identified the S‐nitrosylation sites most likely derived from an increase in nitric oxide (NO) in dependence of presence of AD pathology, age and the key enzyme NOS2. The resulting list of candidate proteins is discussed considering function, previous findings in the context of neurodegeneration, and the potential for further validation studies.

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The pathological roles of NDRG2 in Alzheimer's disease, a study using animal models and APPwt‐overexpressed cells

Abstract: Our study confirmed the upregulation of NDRG2 in AD animal models and demonstrated its important roles in AD pathology. NDRG2 might be a potential target for studying and treatment of AD.

Cited by 27 publications

References 34 publications

Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains

Transcriptomic analysis of probable asymptomatic and symptomatic Alzheimer brains

Identification of novel immune‐relevant drug target genes for Alzheimer's Disease by combining ontology inference with network analysis

Quantitative proteomics of synaptosome S‐nitrosylation in Alzheimer’s disease

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