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The construction of common and specific significance subnetworks of Alzheimer's disease from multiple brain regions.

Kong W, Mou X, Zhang N, Zeng W, Li S, Yang Y - Biomed Res Int (2015)

Bottom Line: In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions.The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis.In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering College, Shanghai Maritime University, Shanghai 201306, China.

ABSTRACT
Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

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Specific subnetwork of EC.
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fig5: Specific subnetwork of EC.

Mentions: In EC area, 40 specially expressed genes were constructed to the maximal scoring subnetwork (Figure 5). The changes in the Tau protein and the cleaved fragments of APP have been found in EC region in the early stages of AD [38]. In this brain area, our data showed that BRAF, C21orf91, CBL, CSF2RB, LYN, MDM2, SLA, and KANK1 were all overexpressed. BRAF, as a member of the RAF kinase family of growth signal transduction protein kinases, can affect cell division, differentiation, and secretion by regulating the MAP kinase/ERKs signaling pathway [39]. Members of the Casitas B-lineage lymphoma (Cbl) protein family are evolutionarily conserved multidomain regulators of signal transduction. Colony stimulating factor 2 receptor β (CSF2RB) is a risk factor in both schizophrenia and major depression since the overexpression of it has relationship with the disturbance of nerve signal conduction [40]. AKT1 is a survival factor and the activated AKT1 plays important roles in inhibiting apoptosis and promoting cell survival [41, 42]. Our results showed that AKT1 was low expressed in EC of AD patients which indicated that apoptosis was happening.


The construction of common and specific significance subnetworks of Alzheimer's disease from multiple brain regions.

Kong W, Mou X, Zhang N, Zeng W, Li S, Yang Y - Biomed Res Int (2015)

Specific subnetwork of EC.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4383160&req=5

fig5: Specific subnetwork of EC.
Mentions: In EC area, 40 specially expressed genes were constructed to the maximal scoring subnetwork (Figure 5). The changes in the Tau protein and the cleaved fragments of APP have been found in EC region in the early stages of AD [38]. In this brain area, our data showed that BRAF, C21orf91, CBL, CSF2RB, LYN, MDM2, SLA, and KANK1 were all overexpressed. BRAF, as a member of the RAF kinase family of growth signal transduction protein kinases, can affect cell division, differentiation, and secretion by regulating the MAP kinase/ERKs signaling pathway [39]. Members of the Casitas B-lineage lymphoma (Cbl) protein family are evolutionarily conserved multidomain regulators of signal transduction. Colony stimulating factor 2 receptor β (CSF2RB) is a risk factor in both schizophrenia and major depression since the overexpression of it has relationship with the disturbance of nerve signal conduction [40]. AKT1 is a survival factor and the activated AKT1 plays important roles in inhibiting apoptosis and promoting cell survival [41, 42]. Our results showed that AKT1 was low expressed in EC of AD patients which indicated that apoptosis was happening.

Bottom Line: In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions.The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis.In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering College, Shanghai Maritime University, Shanghai 201306, China.

ABSTRACT
Alzheimer's disease (AD) is a progressively and fatally neurodegenerative disorder and leads to irreversibly cognitive and memorial damage in different brain regions. The identification and analysis of the dysregulated pathways and subnetworks among affected brain regions will provide deep insights for the pathogenetic mechanism of AD. In this paper, commonly and specifically significant subnetworks were identified from six AD brain regions. Protein-protein interaction (PPI) data were integrated to add molecular biological information to construct the functional modules of six AD brain regions by Heinz algorithm. Then, the simulated annealing algorithm based on edge weight is applied to predicting and optimizing the maximal scoring networks for common and specific genes, respectively, which can remove the weak interactions and add the prediction of strong interactions to increase the accuracy of the networks. The identified common subnetworks showed that inflammation of the brain nerves is one of the critical factors of AD and calcium imbalance may be a link among several causative factors in AD pathogenesis. In addition, the extracted specific subnetworks for each brain region revealed many biologically functional mechanisms to understand AD pathogenesis.

Show MeSH
Related in: MedlinePlus