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Functional analysis and signaling pathway enrichment analysis of genes associated with Alzheimer’s disease and Parkinson’s disease

https://doi.org/10.20538/1682-0363-2020-1-108-113

Abstract

We identified significant functions of susceptibility-genes and performed an analysis of pathway enrichment for Alzheimer’s disease, Parkinson’s disease and for both of them. Genes were extracted from a Catalog of Published Genome-Wide Association Studies (GWAS). We uploaded genes into Cytoscape version 3.2.1. ClueGO plugin was used for functional and pathway enrichment analysis of genes based on the hypergeometric test. Two databases, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and
REACTOME, were selected for analysis.
The identified susceptibility genes are involved in the synthesis regulation and accumulation of toxic proteins,
β-amyloid and α-synuclein, and lead to apoptosis of neurons. We have defined 14 shared functions: collagen catabolic process, cellular response to retinoic acid, regulation of calcium-mediated signaling, negative regulation of cell projection organization, negative regulation of neuron projection development, glial cell activation, microglial cell activation, macrophage activation, regulation of cholesterol metabolism, clathrin-mediated endocytosis, regulation of protein oligomerization, regulation of dendritic spine development, kinesin binding and clathrin binding. Also, we have defined 3 shared signaling pathways: trans-Golgi Network Vesicle Budding, Clathrin derived vesicle budding, Intestinal immune network for IgA production. These pathways contain genes susceptible to Alzheimer’s disease and Parkinson’s disease. The results suggest the metabolic, neuronal and immunological factors participate in the development of Parkinson’s disease and Alzheimer’s disease.

About the Authors

N. Yu. Chasovskikh
Siberian State Medical University
Russian Federation
2, Moscow Trakt, Tomsk, 634050, Russian Federation



A. Yu. Grechishnikova
Siberian State Medical University
Russian Federation
2, Moscow Trakt, Tomsk, 634050, Russian Federation



D. V. Smirnov
Siberian State Medical University
Russian Federation
2, Moscow Trakt, Tomsk, 634050, Russian Federation



References

1. Coskuner-Weber O., Uversky V.N. Insights into the molecular mechanisms of Alzheimer’s and Parkinson’s diseases with molecular simulations: understanding the roles of artificial and pathological missense mutations in intrinsically disordered proteins related to pathology. Int. J. Mol. 2018; 19 (2): 336. DOI: 10.3390/ijms19020336.

2. Zhentao Z., Liu X., Eun Hee Ahn et al. Asparagine endopeptidase cleaves α-synuclein and mediates pathologic activities in Parkinson’s disease. Nature Structural & Molecular Biology. 2017; 24 (8): 632–642. DOI: 10.1038/nsmb.3433.

3. Ping L., Duong D.M., Yin L. et al. Global quantitative analysis of the human brain proteome in Alzheimer’s and Parkinson’s Disease. Sci. Data. 2018; 5: 180036. DOI: 10.1038/sdata.2018.36.

4. Liu G., Bao X., Jiang Y., Feng R. et al. Identifying the Association Between Alzheimer’s Disease and Parkinson’s Disease Using Genome-Wide Association Studies and Protein-Protein Interaction Network. Mol. Neurobiol. 2015; 52 (3): 1629–1636. DOI: 10.1007/s12035-014-8946-8.

5. Huang D.W., Sherman B.T., Lempicki R.A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic. Acids Research. 2009; 37 (1): 1–13. DOI: 10.1093/nar/gkn923.

6. Welter D., MacArthur J., Morales J. et at. The NHGRI GWAS Catalog, a curated resource of SNPtraitassociations. Nucleic Acids Research. 2014; 42: D1001–1006. DOI: 10.1093/nar/gkt1229.

7. Blake A., Christie K.R., Dolan M.E. et al. Gene Ontology Consortium: going forward. Nucleic Acids Research. 2015; 43: D1049–1056. DOI: 10.1093/nar/gku1179.

8. Sim J., Wright C.C. The Kappa Statistic in Reliability Studies: Use, Interpretation, and Sample Size Requirements. Physical Therapy. 2005; 85 (3): 257–268.

9. Martin I., Dawson V.L., Dawson T.M. Recent advances in the genetics of Parkinson’s disease. Annu. Rev. Genomics Hum. Genet. 2011; 12: 301–325. DOI: 10.1146/annurev-genom-082410-101440.

10. Wilhelmus M.M., Jansen Q., Witte M.E. et al. Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions. Free RadicBiol. Med. 2011; 50 (3): 469–476. DOI: 10.1016/j.freeradbiomed.2010.11.033.

11. McKenzie J.A., Spielman L.J., Pointer C.B., Lowry J.R., Bajwa E., Lee C.W., Klegeris A. Neuroinflammation as a сommon mechanism associated with the modifiable risk factors for Alzheimer’s and Parkinson’s diseases. Curr. Aging Sci. 2017; 10 (3): 158–176. DOI: 10.2174/1874609810666170315113244.

12. Wilhelmus M.M., van der Pol S.M., Jansen Q., Witte M.E., van der Valk P., Rozemuller A.J., Drukarch B., de Vries H.E., van Horssen J. Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions. Free RadicBiol. Med. 2011; 50 (3): 469–476. DOI: 10.1016/j.freeradbiomed.2010.11.033.

13. Esteves M., Cristóvã A.C., Saraiva T. et al. Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for Parkinson’s disease. Front Aging Neurosci. 2015; 7: 20. DOI: 10.3389/fnagi.2015.00020.

14. Tong B.C., Wu A.J., Li M., Cheung K.H. Calcium signaling in Alzheimer’s disease & therapies. Biochim. Biophys. Acta Mol. Cell Res. 2018; 1865 (11): 1745–1760. DOI: 10.1016/j.bbamcr.2018.07.018.

15. Wilkinson B., Downey J.S., Rudd C.E. T-cell signalling and immune system disorders. Expert Rev. Mol. Med. 2005; 7 (29): 1–29. DOI: 10.1017/S1462399405010264

16. Paththinige C.S., Sirisena N.D., Dissanayake V. Genetic determinants of inherited susceptibility to hypercholesterolemia – a comprehensive literature review. Lipids Health Dis. 2017; 16 (1): 103. DOI: 10.1186/s12944-017-0488-4.

17. Majd S., Power J.H., Grantham H.J.. Neuronal response in Alzheimer’s and Parkinson’s disease: the effect of toxic proteins on intracellular pathways. BMC Neurosci. 2015; 16: 69. DOI: 10.1186/s12868-015-0211-1.

18. Hu Y.-S., Xin J., Zhang L., Wang J. Analyzing the genes related to Alzheimer’s disease via a network and pathway-based approach. Alzheimer’s Research & Therapy. 2017; 9 (1): 29. DOI: 10.1186/s13195-017-0252-z .


Review

For citations:


Chasovskikh N.Yu., Grechishnikova A.Yu., Smirnov D.V. Functional analysis and signaling pathway enrichment analysis of genes associated with Alzheimer’s disease and Parkinson’s disease. Bulletin of Siberian Medicine. 2020;19(1):108-113. https://doi.org/10.20538/1682-0363-2020-1-108-113

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ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)