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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 PC.
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fig6: Specific subnetwork of PC.

Mentions: Figure 6 shows the maximal scoring subnetwork of PC area constructed by 16 specifically significant genes. PC is a polymodal association area that contributes importantly to normal recognition memory and plays a critical role in visual perception [43, 44]. From Figure 6 we can see that genes CASP3, CASP6, CDKN1A, FLNA, ITGB1, MAPT, PCBP2, PRKACA, and SET were overexpressed in PC area of AD brain. The genes CASP3 and CASP6 are related to apoptosis. CDKN1A (p21) has a function of regulating cell cycle by inhibiting the activity of cyclin-CDK2, cyclin-CDK1, and cyclin-CDK4/6 complexes and it activates CDK2; thus, it leads to apoptosis [45, 46]. The Tau proteins are the product of alternative splicing from a single gene that is designated MAPT (microtubule-associated protein tau) in humans, and the overexpression of Tau will impact a neuroinflammation gene expression network perturbed in AD [2, 47, 48]. The major human AP endonuclease APE1 are reported to play an important role in the base excision repair (BER) pathway [49]; however, they were found to be low expressed in PC area of AD brains.


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 PC.
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Specific subnetwork of PC.
Mentions: Figure 6 shows the maximal scoring subnetwork of PC area constructed by 16 specifically significant genes. PC is a polymodal association area that contributes importantly to normal recognition memory and plays a critical role in visual perception [43, 44]. From Figure 6 we can see that genes CASP3, CASP6, CDKN1A, FLNA, ITGB1, MAPT, PCBP2, PRKACA, and SET were overexpressed in PC area of AD brain. The genes CASP3 and CASP6 are related to apoptosis. CDKN1A (p21) has a function of regulating cell cycle by inhibiting the activity of cyclin-CDK2, cyclin-CDK1, and cyclin-CDK4/6 complexes and it activates CDK2; thus, it leads to apoptosis [45, 46]. The Tau proteins are the product of alternative splicing from a single gene that is designated MAPT (microtubule-associated protein tau) in humans, and the overexpression of Tau will impact a neuroinflammation gene expression network perturbed in AD [2, 47, 48]. The major human AP endonuclease APE1 are reported to play an important role in the base excision repair (BER) pathway [49]; however, they were found to be low expressed in PC area of AD brains.

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