Integrated omics analysis unveils a DNA damage response to neurogenic injury.
Ali Hashemi GheinaniBryan S SackAlex Bigger-AllenHatim ThakerHussein AttaGeorge LambrinosKyle CostaClaire DoyleMehrnaz Gharaee-KermaniSusan PatalanoMary PiperJustin F CotellessaDijana VitkoHaiying LiManubhai Kadayil PrabhakaranVivian CristofaroJohn FroehlichRichard S LeeWei YangMaryrose P SullivanJill A MacoskaRosalyn M AdamPublished in: bioRxiv : the preprint server for biology (2023)
Employed a multi-omics approach, integrating both transcriptomic and proteomic analyses, to investigate the molecular response in a rat model of spinal cord injury (SCI) and the therapeutic effect of inosine.Discovered multiple regulators of the DNA damage response, including PARP-1, using causal network analysis.Observed decreased markers of DNA damage and PARP activity in inosine-treated tissues, indicating the therapeutic potential of inosine in neurogenic dysfunction.Identified significant alterations in molecular pathways associated with protein synthesis, neuroplasticity, wound healing, and neurotransmitter degradation after SCI, and their modulation by inosine, highlighting its neuroprotective effects beyond DNA damage repair.