Skip to content
2000
Volume 25, Issue 5
  • ISSN: 1566-5232
  • E-ISSN: 1875-5631

Abstract

Background

Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the myelin sheath surrounding neuronal axons. While their neuroprotective effects have been demonstrated in Alzheimer's disease, their potential benefits in spinal cord injury remain unexplored. This study investigates the reparative effects of plasmalogens on spinal cord injury and the underlying mechanisms.

Methods

, we developed dorsal root ganglion (DRG) and RAW 264.7 cell models under high-reactive oxygen species (ROS) conditions to assess ROS levels, neuronal damage, and inflammatory microenvironment changes before and after plasmalogen application. , we used a complete mouse spinal cord transection model to evaluate changes in ROS levels, neuronal demyelination, and apoptosis following plasmalogen treatment. Additionally, we assessed sensory and motor function recovery and investigated the regulatory effects of plasmalogens on the AKT/mTOR signaling pathway.

Results

In high-ROS cell models, plasmalogens protected DRG neurons (TUJ-1) from axonal damage and modulated the proinflammatory/anti-inflammatory balance in RAW 264.7 cells. , plasmalogens significantly reduced ROS levels, improved the immune microenvironment, decreased the proinflammatory (iNOS)/anti-inflammatory (ARG-1) ratio, lowered neuronal (TUJ-1) apoptosis (Caspase-3, BAX), and reduced axonal degeneration while promoting myelin (MBP) regeneration, indicating a neuroprotective effect. These findings are linked to the activation of the AKT/mTOR signaling pathway.

Conclusion

Plasmalogens reduce ROS levels and regulate inflammation-induced damage, contributing to neuroprotection. This study reveals that plasmalogens promote remyelination, reduce axonal degeneration and neuronal apoptosis, and—used here for the first time in spinal cord injury repair—may protect neurons by reducing ROS levels and activating the AKT/mTOR signaling pathway.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cgt/10.2174/0115665232330349241225074627
2025-01-20
2025-10-29

  • From This Site

    /content/journals/cgt/10.2174/0115665232330349241225074627
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AssinckP. DuncanG.J. HiltonB.J. PlemelJ.R. TetzlaffW. Cell transplantation therapy for spinal cord injury.Nat. Neurosci.201720563764710.1038/nn.4541 28440805
     [Google Scholar]
  2. HuX. XuW. RenY. Spinal cord injury: Molecular mechanisms and therapeutic interventions.Signal Transduct. Target. Ther.20238124510.1038/s41392‑023‑01477‑6 37357239
     [Google Scholar]
  3. YinZ. WanB. GongG. YinJ. ROS: Executioner of regulating cell death in spinal cord injury.Front. Immunol.202415133067810.3389/fimmu.2024.1330678 38322262
     [Google Scholar]
  4. YingY. HuangZ. TuY. A shear-thinning, ROS-scavenging hydrogel combined with dental pulp stem cells promotes spinal cord repair by inhibiting ferroptosis.Bioact. Mater.20232227429010.1016/j.bioactmat.2022.09.019 36263097
     [Google Scholar]
  5. ZhangY. YangX. GeX. ZhangF. Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice.Biomed. Pharmacother.201910972673310.1016/j.biopha.2018.10.161 30551525
     [Google Scholar]
  6. LiuC. HuF. JiaoG. Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury.J. Nanobiotechnology20222016510.1186/s12951‑022‑01273‑4 35109874
     [Google Scholar]
  7. Freyermuth-TrujilloX. Segura-UribeJ.J. Salgado-CeballosH. Orozco-BarriosC.E. Coyoy-SalgadoA. Inflammation: A target for treatment in spinal cord injury.Cells20221117269210.3390/cells11172692 36078099
     [Google Scholar]
  8. PaulS. LancasterG.I. MeikleP.J. Plasmalogens: A potential therapeutic target for neurodegenerative and cardiometabolic disease.Prog. Lipid Res.20197418619510.1016/j.plipres.2019.04.003 30974122
     [Google Scholar]
  9. LeßigJ. FuchsB. Plasmalogens in biological systems: Their role in oxidative processes in biological membranes, their contribution to pathological processes and aging and plasmalogen analysis.Curr. Med. Chem.200916162021204110.2174/092986709788682164 19519379
     [Google Scholar]
  10. YoussefM. IbrahimA. AkashiK. HossainM.S. PUFA-plasmalogens attenuate the lps-induced nitric oxide production by inhibiting the NF-κB, p38 MAPK and JNK pathways in microglial cells.Neuroscience2019397183010.1016/j.neuroscience.2018.11.030 30496826
     [Google Scholar]
  11. CheH. ZhangL. DingL. EPA-enriched ethanolamine plasmalogen and EPA-enriched phosphatidylethanolamine enhance BDNF/TrkB/CREB signaling and inhibit neuronal apoptosis in vitro and in vivo.Food Funct.20201121729173910.1039/C9FO02323B 32043504
     [Google Scholar]
  12. HossainM.S. MawatariS. FujinoT. Plasmalogens, the vinyl ether-linked glycerophospholipids, enhance learning and memory by regulating brain-derived neurotrophic factor.Front. Cell Dev. Biol.20221082828210.3389/fcell.2022.828282 35223852
     [Google Scholar]
  13. FujinoT. YamadaT. AsadaT. Efficacy and Blood plasmalogen changes by oral administration of plasmalogen in patients with mild Alzheimer’s disease and mild cognitive impairment: A multicenter, randomized, double-blind, placebo-controlled trial.EBioMedicine20171719920510.1016/j.ebiom.2017.02.012 28259590
     [Google Scholar]
  14. XuB. YinM. YangY. Transplantation of neural stem progenitor cells from different sources for severe spinal cord injury repair in rat.Bioact. Mater.20232330031310.1016/j.bioactmat.2022.11.008 36439085
     [Google Scholar]
  15. XiongX.Y. LiuL. YangQ.W. Functions and mechanisms of microglia/macrophages in neuroinflammation and neurogenesis after stroke.Prog. Neurobiol.2016142234410.1016/j.pneurobio.2016.05.001 27166859
     [Google Scholar]
  16. LiL. JiangW. YuB. Quercetin improves cerebral ischemia/reperfusion injury by promoting microglia/macrophages M2 polarization via regulating PI3K/Akt/NF-κB signaling pathway.Biomed. Pharmacother.202316811565310.1016/j.biopha.2023.115653 37812891
     [Google Scholar]
  17. WangD. LiuF. ZhuL. FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages.J. Neuroinflammation202017125710.1186/s12974‑020‑01921‑2 32867781
     [Google Scholar]
  18. TremblayM.È. AlmsherqiZ.A. DengY. Plasmalogens and platelet‐activating factor roles in chronic inflammatory diseases.Biofactors20224861203121610.1002/biof.1916 36370412
     [Google Scholar]
  19. DengS. DaiG. ChenS. Dexamethasone induces osteoblast apoptosis through ROS-PI3K/AKT/GSK3β signaling pathway.Biomed. Pharmacother.201911060260810.1016/j.biopha.2018.11.103 30537677
     [Google Scholar]
  20. LiK. DengY. DengG. High cholesterol induces apoptosis and autophagy through the ROS-activated AKT/FOXO1 pathway in tendon-derived stem cells.Stem Cell Res. Ther.202011113110.1186/s13287‑020‑01643‑5 32197645
     [Google Scholar]
  21. WuL.K. AgarwalS. KuoC.H. Artemisia Leaf Extract protects against neuron toxicity by TRPML1 activation and promoting autophagy/mitophagy clearance in both in vitro and in vivo models of MPP+/MPTP-induced Parkinson’s disease.Phytomedicine202210415425010.1016/j.phymed.2022.154250 35752074
     [Google Scholar]
  22. da SilvaT.F. EiraJ. LopesA.T. Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination.J. Clin. Invest.201412462560257010.1172/JCI72063 24762439
     [Google Scholar]
  23. Ferreira da SilvaT. GranadeiroL.S. Bessa-NetoD. LuzL.L. SafronovB.V. BritesP. Plasmalogens regulate the AKT-ULK1 signaling pathway to control the position of the axon initial segment.Prog. Neurobiol.202120510212310.1016/j.pneurobio.2021.102123 34302896
     [Google Scholar]
  24. HossainM.S. IfukuM. TakeS. KawamuraJ. MiakeK. KatafuchiT. Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling.PLoS One2013812e8350810.1371/journal.pone.0083508 24376709
     [Google Scholar]
  25. YuL. WeiJ. LiuP. Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer.Semin. Cancer Biol.202285699410.1016/j.semcancer.2021.06.019 34175443
     [Google Scholar]
  26. GlavianoA. FooA.S.C. LamH.Y. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.Mol. Cancer202322113810.1186/s12943‑023‑01827‑6 37596643
     [Google Scholar]
  27. HuangY. ZhouJ. LuoS. Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44.Gut201867230731910.1136/gutjnl‑2016‑311909 27849558
     [Google Scholar]
  28. DorvashM. FarahmandniaM. TavassolyI. A Systems biology roadmap to decode mTOR control system in cancer.Interdiscip. Sci.202012111110.1007/s12539‑019‑00347‑6 31531812
     [Google Scholar]
  29. Marques-RamosA. CervantesR. Expression of mTOR in normal and pathological conditions.Mol. Cancer202322111210.1186/s12943‑023‑01820‑z 37454139
     [Google Scholar]
  30. DingY. ChenQ. mTOR pathway: A potential therapeutic target for spinal cord injury.Biomed. Pharmacother.202214511243010.1016/j.biopha.2021.112430 34800780
     [Google Scholar]
  31. ChenK ZhengY WeiJ Exercise training improves motor skill learning via selective activation of mTOR.Sci Adv201957eaaw188810.1126/sciadv.aaw1888
     [Google Scholar]
  32. ZhiS-M. FangG-X. XieX-M. Melatonin reduces OGD/R-induced neuron injury by regulating redox/inflammation/apoptosis signaling.Eur. Rev. Med. Pharmacol. Sci.202024315241536 32096202
     [Google Scholar]
  33. WalkerC.L. WuX. LiuN.K. XuX.M. Bisperoxovanadium mediates neuronal protection through inhibition of PTEN and activation of PI3K/AKT-mTOR signaling after traumatic spinal injuries.J. Neurotrauma201936182676268710.1089/neu.2018.6294 30672370
     [Google Scholar]
  34. MiaoL. YangL. HuangH. LiangF. LingC. HuY. mTORC1 is necessary but mTORC2 and GSK3β are inhibitory for AKT3-induced axon regeneration in the central nervous system.eLife20165e1490810.7554/eLife.14908 27026523
     [Google Scholar]
  35. SternerR.C. SternerR.M. Immune response following traumatic spinal cord injury: Pathophysiology and therapies.Front. Immunol.202313108410110.3389/fimmu.2022.1084101 36685598
     [Google Scholar]
/content/journals/cgt/10.2174/0115665232330349241225074627
Loading
Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury
Curr. Gene Ther. 25, 718 (2025); https://doi.org/10.2174/0115665232330349241225074627
/content/journals/cgt/10.2174/0115665232330349241225074627
/content/journals/cgt/10.2174/0115665232330349241225074627
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): AKT/mTOR; neuronal apoptosis; Plasmalogens; ROS; spinal cord injury; trauma

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test