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

International Journal of Molecular Sciences
Jure TicaAthanasios Didangelos

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-po...Continue Reading

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Citations

Jan 5, 2020·Molecular Neurobiology·Tasneem Ismail KhanMohammad Waseem
Apr 25, 2020·Molecular Neurobiology·Hadi Abou-El-HassanIbrahim Omeis
Apr 25, 2020·Cells·Valeria De PasqualeLuigi Michele Pavone
Oct 20, 2018·International Journal of Molecular Sciences·Pavla Jendelova
May 19, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xin ZhouDachuan Wang

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