Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease

Liang, Dapeng; Han, Guangchun; Feng, Xiao; Sun, Jiya; Duan, Yong; Lei, Hongxing

doi:10.1371/journal.pone.0040498

Cited by 70 publications

(50 citation statements)

References 143 publications

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“…Among them, the glucose transport regulator astrocytic phosphoprotein PEA-15 (PEA-15) protein may play a protective role in AD (Ahn et al, 2014) and is able to bind to MAP2K1. MAP2K1 phosphorylation drives cytoplasmic accumulation of heterogeneous nuclear ribonucleoprotein K (HNRPK or HNRNPK) synaptic transmission and spine development regulator protein (Habelhah et al, 2001), whose expression pattern is also correlated with AD progression (Liang et al, 2012).…”

Section: Relationships Of Chronic Cerebral Hypoperfusion Altered Synamentioning

confidence: 99%

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

et al. 2017

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Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH 2 induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established.In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with Magnetic Resonance Angiography 5 weeks after the surgery.Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analysed with label free nanoUHPLC-MS/MS.

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Section: Relationships Of Chronic Cerebral Hypoperfusion Altered Synamentioning

confidence: 99%

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

et al. 2017

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“…AD is a complex disease, and many factors may affect the gene expression patterns, such as brain region, age as well as the degree of brain destruction (Braak and Braak (B&B) stage). However, several studies have suggested that certain important common features could be shared among different regions in AD brain [29][30][31]. In this study, to investigate the commonality among AD subjects and to obtain stable and consistently differentially expressed genes (CDGs), we used meta-analysis to detect differential expression in nine case-control studies that correspond to different microarray studies (table 1).…”

Section: Methodsmentioning

confidence: 99%

Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease

Meng

Dai

et al. 2014

J. R. Soc. Interface.

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Alzheimer's disease (AD) is an incurable neurodegenerative disorder. Much effort has been devoted to developing effective therapeutic agents. Recently, targeting microRNAs (miRNAs) with small molecules has become a novel therapy for human diseases. In this study, we present a systematic computational approach to construct a bioactive Small molecule and miRNA association Network in AD (SmiRN-AD), which is based on the gene expression signatures of bioactive small molecule perturbation and AD-related miRNA regulation. We also performed topological and functional analysis of the SmiRN-AD from multiple perspectives. At the significance level of p ≤ 0.01, 496 small molecule–miRNA associations, including 25 AD-related miRNAs and 275 small molecules, were recognized and used to construct the SmiRN-AD. The drugs that were connected with the same miRNA tended to share common drug targets ( p = 1.72 × 10 −4 ) and belong to the same therapeutic category ( p = 4.22 × 10 −8 ). The miRNAs that were linked to the same small molecule regulated more common miRNA targets ( p = 6.07 × 10 −3 ). Further analysis of the positive connections (quinostatin and miR-148b, amantadine and miR-15a) and the negative connections (melatonin and miR-30e-5p) indicated that our large-scale predictions afforded specific biological insights into AD pathogenesis and therapy. This study proposes a holistic strategy for deciphering the associations between small molecules and miRNAs in AD, which may be helpful for developing a novel effective miRNA-associated therapeutic strategy for AD. A comprehensive database for the SmiRN-AD and the differential expression patterns of the miRNA targets in AD is freely available at http://bioinfo.hrbmu.edu.cn/SmiRN-AD/ .

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“…A relationship has been identified between the cognitive and behavioral symptoms of AD and the dysfunction of certain brain regions (Liang et al, 2008a). A comprehensive study carried out by Liang et al (2012) based the identification of the most critical dysregulated genes in six different AD-relevant brain regions on a sub-graph algorithm. However, this study only analyzed one dataset for each brain region and ignored the large body of research that has focused on one particular brain region.…”

Section: Introductionmentioning

confidence: 99%

Potential hippocampal genes and pathways involved in Alzheimer’s disease: a bioinformatic analysis

Zhang¹,

Guo²,

Chu³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in elderly people. Numerous studies have focused on the dysregulated genes in AD, but the pathogenesis is still unknown. In this study, we explored critical hippocampal genes and pathways that might potentially be involved in the pathogenesis of AD. Four transcriptome datasets for the hippocampus of patients with AD were downloaded from ArrayExpress, and the gene signature was identified by integrated analysis of multiple transcriptomes using novel genome-wide relative significance and genome-wide global significance models. A protein-protein interaction network was constructed, and five clusters were selected. The biological functions and pathways were identified by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 6994 genes were screened, and the top 300 genes were subjected to further analysis. Four significant KEGG pathways were identified, including oxidative phosphorylation and Parkinson's (2015) disease, Huntington's disease, and Alzheimer's disease pathways. The hub network of cluster 1 with the highest average rank value was defined. The genes (NDUFB3, NDUFA9, NDUFV1, NDUFV2, NDUFS3, NDUFA10, COX7B, and UQCR1) were considered critical with high degree in cluster 1 as well as being shared by the four significant pathways. The oxidative phosphorylation process was also involved in the other three pathways and is considered to be relevant to energy-related AD pathology in the hippocampus. This research provides a perspective from which to explore critical genes and pathways for potential AD therapies.

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Concerted Perturbation Observed in a Hub Network in Alzheimer’s Disease

Cited by 70 publications

References 143 publications

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease

Potential hippocampal genes and pathways involved in Alzheimer’s disease: a bioinformatic analysis

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