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Int. J. Mol. Sci. 2018, 19(5), 1461; https://doi.org/10.3390/ijms19051461

Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury

1
Imperial College London, Alexander Fleming Building, London SW7 2AZ, UK
2
King’s College London, Wolfson CARD, Institute of Psychiatry, Psychology & Neuroscience, London SE1 1UL, UK
3
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester LE1 7RH, UK
*
Author to whom correspondence should be addressed.
Received: 31 January 2018 / Revised: 6 April 2018 / Accepted: 9 April 2018 / Published: 14 May 2018
(This article belongs to the Special Issue Therapeutic Strategies to Spinal Cord Injury)
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Abstract

Spinal cord injury (SCI) causes irreversible tissue damage and severe loss of neurological function. Currently, there are no approved treatments and very few therapeutic targets are under investigation. Here, we combined 4 high-throughput transcriptomics and proteomics datasets, 7 days and 8 weeks following clinically-relevant rat SCI to identify proteins with persistent differential expression post-injury. Out of thousands of differentially regulated entities our combined analysis identified 40 significantly upregulated versus 48 significantly downregulated molecules, which were persistently altered at the mRNA and protein level, 7 days and 8 weeks post-SCI. Bioinformatics analysis was then utilized to identify currently available drugs with activity against the filtered molecules and to isolate proteins with known or unknown function in SCI. Our findings revealed multiple overlooked therapeutic candidates with important bioactivity and established druggability but with unknown expression and function in SCI including the upregulated purine nucleoside phosphorylase (PNP), cathepsins A, H, Z (CTSA, CTSH, CTSZ) and proteasome protease PSMB10, as well as the downregulated ATP citrate lyase (ACLY), malic enzyme (ME1) and sodium-potassium ATPase (ATP1A3), amongst others. This work reveals previously unappreciated therapeutic candidates for SCI and available drugs, thus providing a valuable resource for further studies and potential repurposing of existing therapeutics for SCI. View Full-Text
Keywords: spinal cord injury; transcriptomics; proteomics; bioinformatics spinal cord injury; transcriptomics; proteomics; bioinformatics
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Tica, J.; Bradbury, E.J.; Didangelos, A. Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury. Int. J. Mol. Sci. 2018, 19, 1461.

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