D-4F, an apolipoprotein A-I mimetic, promotes the clearance of myelin debris and the reduction of foamy macrophages after spinal cord injury

Abstract

After spinal cord injury (SCI), a large number of blood-derived macrophages infiltrate the lesion site and phagocytose myelin debris to become foamy macrophages, which leads to chronic inflammation. The drug D-4F, an apolipoprotein A-I peptidomimetic made of D-amino acids, has been reported to promote the lipid metabolism of foamy macrophages in atherosclerosis. However, the role and mechanism of D-4F in SCI are still unclear. In this study, we found that D-4F can promote the removal of myelin debris, reduce the formation of foamy macrophages in the lesion core and promote neuroprotection and recovery of motor function after SCI. These beneficial functions of D-4F may be related to its ability to upregulate the expression of ATP-binding cassette transporter A1 (ABCA1), the main transporter that mediates lipid efflux in foamy macrophages because inhibiting the activity of ABCA1 can reverse the effect of D-4F in vitro . In conclusion, D-4F may be a promising candidate for treating SCI by promoting the clearance of myelin debris by foamy macrophages via the ABCA1 pathway.

The role of foam cells in spinal cord injury: challenges and opportunities for intervention

“…Currently, there is still no systematic summary of ApoA-I expression levels after spinal cord injury, and there are few relevant interventions. An ApoA-I peptide mimetic made from D-amino acids, D-4F, improved HDL-mediated cholesterol efflux from macrophages and reduced foam cell formation in spinal cord injury ( 113 ). Notably, given the synergistic role that ABCA1 and ABCG1 proteins play with ApoA-I and, as subsequently described, ApoE during lipid efflux, their simultaneous intervention may have a better effect on foam cell formation and accumulation.…”