Toxic aldehyde-scavenging polypeptides mitigate secondary injury after spinal cord injury

Neuroprotective therapy for traumatic spinal cord injury (SCI) still faces formidable challenges in clinic. Immediately after traumatic SCI, toxic reactive aldehydes are largely produced by lipid peroxidation, which subsequently promotes a vicious cycle of oxidative stress and inflammation in injured spinal cord, leading to the worse secondary injury. Therefore, scavenging of toxic reactive aldehydes has become a promising strategy for treatment of secondary SCI. Here, a drug-free polypeptide (PPAH) containing hydrazide groups on the side chains is designed and synthesized for mitigating secondary SCI through scavenging toxic aldehydes. The prepared PPAH displayed the ability to scavenge reactive aldehydes both in vitro and in vivo . Specifically, PPAH exhibited a protective effect against acrolein-induced damage in neurocytes and the intrathecal injection of PPAH was able to suppress inflammation, protect neurons, inhibit demyelination and improve hindlimb functional recovery in a rat SCI model. Therefore, as an effective toxic aldehyde-scavenging agent, PPAH shows promising perspectives in therapies for SCI.