Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury.pdf (3.38 MB)
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Combined Transcriptomics, Proteomics and Bioinformatics Identify Drug Targets in Spinal Cord Injury.

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journal contribution
posted on 31.07.2018, 08:39 by Jure Tica, Elizabeth J. Bradbury, Athanasios Didangelos
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.

Funding

This work was funded by the RoseTrees Trust (M276 and A1384) to Athanasios Didangelos and Elizabeth J. Bradbury; EU 7th framework program (PrimeXS 0220) to Athanasios Didangelos; the Medical Research Council (MRC; SNCF G1002055) to Elizabeth J. Bradbury); MRC and EU funded MR/R005532/1 ERA-NET NEURON to Elizabeth J. Bradbury and Athanasios Didangelos. Athanasios Didangelos was funded by the London Law Trust and King’s College London.

History

Citation

International Journal of Molecular Sciences, 2018, 19 (5), 1461

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

International Journal of Molecular Sciences

Publisher

MDPI

issn

1661-6596

eissn

1422-0067

Acceptance date

09/04/2018

Copyright date

2018

Available date

31/07/2018

Publisher version

http://www.mdpi.com/1422-0067/19/5/1461

Language

en

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