Combined transcriptomics, proteomics and bioinformatics identify drug targets in spinal cord injury
File(s)ijms-19-01461.pdf (3.77 MB)
Published version
OA Location
Author(s)
Tica, Jure
Bradbury, Elizabeth
Didangelos, Athanasios
Type
Journal Article
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.
Date Issued
2018-05-14
Date Acceptance
2018-04-09
Citation
International Journal of Molecular Sciences, 2018, 19 (5), pp.1-19
ISSN
1422-0067
Publisher
MDPI AG
Start Page
1
End Page
19
Journal / Book Title
International Journal of Molecular Sciences
Volume
19
Issue
5
Copyright Statement
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
article distributed under the terms and conditions of the Creative Commons Attribution
(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.mdpi.com/1422-0067/19/5/1461
Subjects
Chemical Physics
0399 Other Chemical Sciences
0604 Genetics
0699 Other Biological Sciences
Publication Status
Published
Date Publish Online
2018-05-14