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Article

Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways

1
Department of Bioinformatics, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus
2
Department of Neurogenetics, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus
3
The Cyprus School of Molecular Medicine, The Cyprus Institute of Neurology and Genetics, Nicosia 2370, Cyprus
4
Institute for Fundamental Biomedical Research, BSRC “Alexander Fleming”, 16672 Vari, Greece
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(18), 6722; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186722
Received: 18 August 2020 / Revised: 4 September 2020 / Accepted: 9 September 2020 / Published: 14 September 2020
Spastic ataxia (SA) is a group of rare neurodegenerative diseases, characterized by mixed features of generalized ataxia and spasticity. The pathogenetic mechanisms that drive the development of the majority of these diseases remain unclear, although a number of studies have highlighted the involvement of mitochondrial and lipid metabolism, as well as calcium signaling. Our group has previously published the GBA2 c.1780G > C (p.Asp594His) missense variant as the cause of spastic ataxia in a Cypriot consanguineous family, and more recently the biochemical characterization of this variant in patients’ lymphoblastoid cell lines. GBA2 is a crucial enzyme of sphingolipid metabolism. However, it is unknown if GBA2 has additional functions and therefore additional pathways may be involved in the disease development. The current study introduces bioinformatics approaches to better understand the pathogenetic mechanisms of the disease. We analyzed publicly available human gene expression datasets of diseases presented with ‘ataxia’ or ‘spasticity’ in their clinical phenotype and we performed pathway analysis in order to: (a) search for candidate perturbed pathways of SA; and (b) evaluate the role of sphingolipid signaling pathway and sphingolipid metabolism in the disease development, through the identification of differentially expressed genes in patients compared to controls. Our results demonstrate consistent differential expression of genes that participate in the sphingolipid pathways and highlight alterations in the pathway level that might be associated with the disease phenotype. Through enrichment analysis, we discuss additional pathways that are connected to sphingolipid pathways, such as PI3K-Akt signaling, MAPK signaling, calcium signaling, and lipid and carbohydrate metabolism as the most enriched for ataxia and spasticity phenotypes. View Full-Text
Keywords: spastic ataxia; gene expression; differential expression; pathway; pathway analysis; neurodegeneration; sphingolipid spastic ataxia; gene expression; differential expression; pathway; pathway analysis; neurodegeneration; sphingolipid
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MDPI and ACS Style

Kakouri, A.C.; Votsi, C.; Tomazou, M.; Minadakis, G.; Karatzas, E.; Christodoulou, K.; Spyrou, G.M. Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways. Int. J. Mol. Sci. 2020, 21, 6722. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186722

AMA Style

Kakouri AC, Votsi C, Tomazou M, Minadakis G, Karatzas E, Christodoulou K, Spyrou GM. Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways. International Journal of Molecular Sciences. 2020; 21(18):6722. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186722

Chicago/Turabian Style

Kakouri, Andrea C., Christina Votsi, Marios Tomazou, George Minadakis, Evangelos Karatzas, Kyproula Christodoulou, and George M. Spyrou 2020. "Analyzing Gene Expression Profiles from Ataxia and Spasticity Phenotypes to Reveal Spastic Ataxia Related Pathways" International Journal of Molecular Sciences 21, no. 18: 6722. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186722

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