Skip to content
2000
Volume 23, Issue 10
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Neuroprotectin D1 (NPD1) has emerged as an integral lipid mediator with significant implications for maintaining neurological health. Being derived from docosahexaenoic acid (DHA), NPD1 is a specialized pro-resolving lipid mediator (SPM), consisting of a unique structure that attributes potent anti-inflammatory and neuroprotective properties crucial for maintaining nervous system homeostasis. It exerts its actions through diverse mechanisms, including the inhibition of proinflammatory cytokines, modulation of apoptosis, and promotion of cellular survival pathways. The dysregulation or deficiency of NPD1 has been implicated in the onset and progression of several neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and stroke, underscoring its critical role in maintaining neuronal health and disease prevention. Abnormal NPD1 signalling is associated with neuroinflammation, oxidative stress, and neuronal apoptosis, which in turn contribute significantly to the progression of neurological disorders. Understanding these pathways offers insights into potential therapeutic strategies aimed at targeting NPD1 to mitigate neurodegenerative processes and facilitate neural repair. The efforts in developing NPD1 analogs or mimetics are focused on enhancing endogenous NPD1 levels, attenuating neuroinflammation, and preserving neuronal integrity in disease contexts. This review provides a comprehensive exploration of NPD1, encompassing its structural characteristics, biochemical pathways, physiological roles, pathophysiological implications, and potential therapeutic applications in neurological disorders. Further, research into elucidating the precise mechanisms of NPD1 reveals that its clinical efficacy is crucial for harnessing its full potential as a therapeutic tool for neuroprotection and neural repair.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cn/10.2174/011570159X365720250225080257
2025-04-07
2025-10-24

  • From This Site

    /content/journals/cn/10.2174/011570159X365720250225080257
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MiyazawaK. Alzheimer's disease and specialized pro-resolving lipid mediators: Ao MaR1, RvD1, and NPD1 show promise for prevention and treatment?Int. J. Mol. Sci.20202116578310.3390/ijms21165783
     [Google Scholar]
  2. MukherjeeP.K. MarcheselliV.L. SerhanC.N. BazanN.G. Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress.Proc. Natl. Acad. Sci. USA2004101228491849610.1073/pnas.040253110115152078
     [Google Scholar]
  3. CalderP.C. Polyunsaturated fatty acids and inflammation.Prostaglandins Leukot. Essent. Fatty Acids200675319720210.1016/j.plefa.2006.05.01216828270
     [Google Scholar]
  4. SerhanC.N. YacoubianS. YangR. Anti-inflammatory and proresolving lipid mediators.Annu. Rev. Pathol. Mech. Dis.2008327931210.1146/annurev.pathmechdis.3.121806.151409
     [Google Scholar]
  5. LevyB.D. ClishC.B. SchmidtB. GronertK. SerhanC.N. Lipid mediator class switching during acute inflammation: Aignals in resolution.Nat. Immunol.20012761261910.1038/8975911429545
     [Google Scholar]
  6. SamuelssonB. DahlénS.E. LindgrenJ.Å. RouzerC.A. SerhanC.N. Leukotrienes and lipoxins: Atructures, biosynthesis, and biological effects.Science198723748191171117610.1126/science.28200552820055
     [Google Scholar]
  7. BuckleyC.D. GilroyD.W. SerhanC.N. StockingerB. TakP.P. The resolution of inflammation.Nat. Rev. Immunol.2013131596610.1038/nri336223197111
     [Google Scholar]
  8. MorrisT. RajakariarR. StablesM. GilroyD.W. Not all eicosanoids are bad.Trends Pharmacol. Sci.2006271260961110.1016/j.tips.2006.10.00117055068
     [Google Scholar]
  9. MarcheselliV.L. HongS. LukiwW.J. TianX.H. GronertK. MustoA. HardyM. GimenezJ.M. ChiangN. SerhanC.N. BazanN.G. Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression.J. Biol. Chem.200327844438074381710.1074/jbc.M30584120012923200
     [Google Scholar]
  10. StarkD.T. BazanN.G. Neuroprotectin D1 induces neuronal survival and downregulation of amyloidogenic processing in Alzheimer’s disease cellular models.Mol. Neurobiol.201143213113810.1007/s12035‑011‑8174‑421431475
     [Google Scholar]
  11. BazanH.E.P. BirkleD.L. BeuermanR.W. BazanN.G. Inflammation-induced stimulation of the synthesis of prostaglandins and lipoxygenase-reaction products in rabbit cornea.Curr. Eye Res.19854317517910.3109/027136885090008473926383
     [Google Scholar]
  12. HongS. GronertK. DevchandP.R. MoussignacR.L. SerhanC.N. Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation.J. Biol. Chem.200327817146771468710.1074/jbc.M30021820012590139
     [Google Scholar]
  13. ArielA. LiP.L. WangW. TangW.X. FredmanG. HongS. GotlingerK.H. SerhanC.N. The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering.J. Biol. Chem.200528052430794308610.1074/jbc.M50979620016216871
     [Google Scholar]
  14. SerhanC.N. GotlingerK. HongS. LuY. SiegelmanJ. BaerT. YangR. ColganS.P. PetasisN.A. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and its natural stereoisomers: Assignments of dihydroxy-containing docosatrienes.J. Immunol.200617631848185910.4049/jimmunol.176.3.184816424216
     [Google Scholar]
  15. TungenJ.E. AursnesM. VikA. RamonS. ColasR.A. DalliJ. SerhanC.N. HansenT.V. Synthesis and anti-inflammatory and pro-resolving activities of 22-OH-PD1, a monohydroxylated metabolite of protectin D1.J. Nat. Prod.201477102241224710.1021/np500498j25247845
     [Google Scholar]
  16. CalandriaJ.M. MarcheselliV.L. MukherjeeP.K. UddinJ. WinklerJ.W. PetasisN.A. BazanN.G. Selective survival rescue in 15-lipoxygenase-1-deficient retinal pigment epithelial cells by the novel docosahexaenoic acid-derived mediator, neuroprotectin D1.J. Biol. Chem.200928426178771788210.1074/jbc.M109.00398819403949
     [Google Scholar]
  17. SapiehaP. 5-lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic effect of ω-3 polyunsaturated fatty acids.Sci. Transl. Med.201136969ra1210.1126/scitranslmed.3001571
     [Google Scholar]
  18. AveldañoM.I. SprecherH. Synthesis of hydroxy fatty acids from 4, 7, 10, 13, 16, 19-[1-14C] docosahexaenoic acid by human platelets.J. Biol. Chem.1983258159339934310.1016/S0021‑9258(17)44672‑26223928
     [Google Scholar]
  19. González-PérizA. PlanagumàA. GronertK. MiquelR. López-ParraM. TitosE. HorrilloR. FerréN. DeulofeuR. ArroyoV. RodésJ. ClàriaJ. González-PérizA. PlanagumàA. GronertK. MiquelR. López-ParraM. TitosE. HorrilloR. FerréN. DeulofeuR. ArroyoV. RodésJ. ClàriaJ. Docosahexaenoic acid (DHA) blunts liver injury by conversion to protective lipid mediators: Arotectin D1 and 17S‐hydroxy‐DHA.FASEB J.200620142537253910.1096/fj.06‑6250fje17056761
     [Google Scholar]
  20. LagardeM. VéricelE. LiuM. ChenP. GuichardantM. Structure-function relationships of non-cyclic dioxygenase products from polyunsaturated fatty acids: Poxytrins as a class of bioactive derivatives.Biochimie2014107Pt A919410.1016/j.biochi.2014.09.00825223888
     [Google Scholar]
  21. HaeggströmJ.Z. FunkC.D. Lipoxygenase and leukotriene pathways: Biochemistry, biology, and roles in disease.Chem. Rev.2011111105866589810.1021/cr200246d21936577
     [Google Scholar]
  22. BrashA.R. Investigation of a second 15s-lipoxygenase in humans and its expression in epithelial tissues.Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 4. HonnK.V. MarnettL.J. NigamS. DennisE.A. Boston, MASpringer US1999838910.1007/978‑1‑4615‑4793‑8_13
     [Google Scholar]
  23. SerhanC.N. PetasisN.A. Resolvins and protectins in inflammation resolution.Chem. Rev.2011111105922594310.1021/cr100396c21766791
     [Google Scholar]
  24. SerhanC.N. HongS. GronertK. ColganS.P. DevchandP.R. MirickG. MoussignacR.L. Resolvins.J. Exp. Med.200219681025103710.1084/jem.2002076012391014
     [Google Scholar]
  25. BannenbergG.L. ChiangN. ArielA. AritaM. TjonahenE. GotlingerK.H. HongS. SerhanC.N. Molecular circuits of resolution: Formation and actions of resolvins and protectins.J. Immunol.200517474345435510.4049/jimmunol.174.7.434515778399
     [Google Scholar]
  26. AursnesM. TungenJ.E. ColasR.A. VlasakovI. DalliJ. SerhanC.N. HansenT.V. Synthesis of the 16 S, 17 S -epoxyprotectin intermediate in the biosynthesis of protectins by human macrophages.J. Nat. Prod.201578122924293110.1021/acs.jnatprod.5b0057426580578
     [Google Scholar]
  27. Stenvik HaatveitÅ. HansenT.V. The biosynthetic pathways of the protectins.Prostaglandins Other Lipid Mediat.202316910678710.1016/j.prostaglandins.2023.10678737806439
     [Google Scholar]
  28. FreedmanC. TranA. TourdotB.E. KalyanaramanC. PerryS. HolinstatM. JacobsonM.P. HolmanT.R. Biosynthesis of the maresin intermediate, 13S,14S-Epoxy-DHA, by human 15-lipoxygenase and 12-lipoxygenase and its regulation through negative allosteric modulators.Biochemistry202059191832184410.1021/acs.biochem.0c0023332324389
     [Google Scholar]
  29. KutznerL. GoloshchapovaK. HeydeckD. StehlingS. KuhnH. SchebbN.H. Mammalian ALOX15 orthologs exhibit pronounced dual positional specificity with docosahexaenoic acid.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20171862766667510.1016/j.bbalip.2017.04.00128400162
     [Google Scholar]
  30. ChenP. FenetB. MichaudS. TomczykN. VéricelE. LagardeM. GuichardantM. Full characterization of PDX, a neuroprotectin/protectin D1 isomer, which inhibits blood platelet aggregation.FEBS Lett.2009583213478348410.1016/j.febslet.2009.10.00419818771
     [Google Scholar]
  31. TsaiW.C. KalyanaramanC. YamaguchiA. HolinstatM. JacobsonM.P. HolmanT.R. In vitro biosynthetic pathway investigations of Neuroprotectin D1 (NPD1) and Protectin DX (PDX) by human 12-Lipoxygenase, 15-Lipoxygenase-1, and 15-Lipoxygenase-2.Biochemistry202160221741175410.1021/acs.biochem.0c0093134029049
     [Google Scholar]
  32. ZhaoY. CalonF. JulienC. WinklerJ.W. PetasisN.A. LukiwW.J. BazanN.G. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer’s disease models.PLoS One201161e1581610.1371/journal.pone.001581621246057
     [Google Scholar]
  33. CampbellI.L. Transgenic mice and cytokine actions in the brain: Aridging the gap between structural and functional neuropathology1Published on the World Wide Web on 21 October 1997.1.Brain Res. Brain Res. Rev.1998262-332733610.1016/S0165‑0173(97)00038‑69651549
     [Google Scholar]
  34. CampbellI.L. AbrahamC.R. MasliahE. KemperP. InglisJ.D. OldstoneM.B. MuckeL. Neurologic disease induced in transgenic mice by cerebral overexpression of interleukin 6.Proc. Natl. Acad. Sci. USA19939021100611006510.1073/pnas.90.21.100617694279
     [Google Scholar]
  35. LeveugleB. FillitH. Proteoglycans and the acute-phase response in Alzheimer’s disease brain.Mol. Neurobiol.199491-3253210.1007/BF028161027888102
     [Google Scholar]
  36. GriffinW.S.T. ShengJ.G. RoystonM.C. GentlemanS.M. McKenzieJ.E. GrahamD.I. RobertsG.W. MrakR.E. Glial-neuronal interactions in Alzheimer’s disease: The potential role of a ‘cytokine cycle’ in disease progression.Brain Pathol.199881657210.1111/j.1750‑3639.1998.tb00136.x9458167
     [Google Scholar]
  37. SarnicoI. LanzillottaA. BoroniF. BenareseM. AlghisiM. SchwaningerM. IntaI. BattistinL. SpanoP. PizziM. NF‐κB p50/RelA and c‐Rel‐containing dimers: Opposite regulators of neuron vulnerability to ischaemia.J. Neurochem.2009108247548510.1111/j.1471‑4159.2008.05783.x19094066
     [Google Scholar]
  38. LukiwW.J. AlexandrovP.N. Regulation of complement factor H (CFH) by multiple miRNAs in Alzheimer’s disease (AD) brain.Mol. Neurobiol.2012461111910.1007/s12035‑012‑8234‑422302353
     [Google Scholar]
  39. ZhaoY. BhattacharjeeS. JonesB.M. HillJ. DuaP. LukiwW.J. Regulation of neurotropic signaling by the inducible, NF-κB-sensitive miRNA-125b in Alzheimer’s disease (AD) and in primary human neuronal-glial (HNG) cells.Mol. Neurobiol.20145019710610.1007/s12035‑013‑8595‑324293102
     [Google Scholar]
  40. FeoktistovaM. GeserickP. KellertB. DimitrovaD.P. LanglaisC. HupeM. CainK. MacFarlaneM. HäckerG. LeverkusM. cIAPs block Ripoptosome formation, a RIP1/caspase-8 containing intracellular cell death complex differentially regulated by cFLIP isoforms.Mol. Cell201143344946310.1016/j.molcel.2011.06.01121737330
     [Google Scholar]
  41. TenevT. BianchiK. DardingM. BroemerM. LanglaisC. WallbergF. ZachariouA. LopezJ. MacFarlaneM. CainK. MeierP. The Ripoptosome, a signaling platform that assembles in response to genotoxic stress and loss of IAPs.Mol. Cell201143343244810.1016/j.molcel.2011.06.00621737329
     [Google Scholar]
  42. CalandriaJ.M. AsatryanA. BalaszczukV. KnottE.J. JunB.K. MukherjeeP.K. BelayevL. BazanN.G. NPD1-mediated stereoselective regulation of BIRC3 expression through cREL is decisive for neural cell survival.Cell Death Differ.20152281363137710.1038/cdd.2014.23325633199
     [Google Scholar]
  43. FengC. HeJ. ZhangY. LanM. YangM. LiuH. HuangB. PanY. ZhouY. Collagen-derived N-acetylated proline-glycine-proline upregulates the expression of pro-inflammatory cytokines and extracellular matrix proteases in nucleus pulposus cells via the NF-κB and MAPK signaling pathways.Int. J. Mol. Med.201740116417410.3892/ijmm.2017.300528560408
     [Google Scholar]
  44. SunE. MotolaniA. CamposL. LuT. The pivotal role of NF-kB in the pathogenesis and therapeutics of Alzheimer’s disease.Int. J. Mol. Sci.20222316897210.3390/ijms2316897236012242
     [Google Scholar]
  45. KettenmannH. KirchhoffF. VerkhratskyA. Microglia: New roles for the synaptic stripper.Neuron2013771101810.1016/j.neuron.2012.12.02323312512
     [Google Scholar]
  46. ClausenB.H. LambertsenK.L. BabcockA.A. HolmT.H. Dagnaes-HansenF. FinsenB. Interleukin-1beta and tumor necrosis factor-alpha are expressed by different subsets of microglia and macrophages after ischemic stroke in mice.J. Neuroinflammation2008514610.1186/1742‑2094‑5‑4618947400
     [Google Scholar]
  47. LiddelowS.A. GuttenplanK.A. ClarkeL.E. BennettF.C. BohlenC.J. SchirmerL. BennettM.L. MünchA.E. ChungW.S. PetersonT.C. WiltonD.K. FrouinA. NapierB.A. PanickerN. KumarM. BuckwalterM.S. RowitchD.H. DawsonV.L. DawsonT.M. StevensB. BarresB.A. Neurotoxic reactive astrocytes are induced by activated microglia.Nature2017541763848148710.1038/nature2102928099414
     [Google Scholar]
  48. Gómez-GalánM. De BundelD. Van EeckhautA. SmoldersI. LindskogM. Dysfunctional astrocytic regulation of glutamate transmission in a rat model of depression.Mol. Psychiatry201318558259410.1038/mp.2012.1022371047
     [Google Scholar]
  49. ZhouY. WangJ. LiX. LiK. ChenL. ZhangZ. PengM. Neuroprotectin D1 protects against postoperative delirium-like behavior in aged mice.Front. Aging Neurosci.20201258267410.3389/fnagi.2020.58267433250764
     [Google Scholar]
  50. ChiangN. FredmanG. BäckhedF. OhS.F. VickeryT. SchmidtB.A. SerhanC.N. Infection regulates pro-resolving mediators that lower antibiotic requirements.Nature2012484739552452810.1038/nature1104222538616
     [Google Scholar]
  51. ChengY. RongJ. Pro-resolving lipid mediators as therapeutic leads for cardiovascular diseases.Expert Opin. Ther. Targets201923542343610.1080/14728222.2019.159936030917700
     [Google Scholar]
  52. AntonyR. LukiwW.J. BazanN.G. Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival.J. Biol. Chem.201028524183011830810.1074/jbc.M109.09523220363734
     [Google Scholar]
  53. SerhanC.N. DalliJ. ColasR.A. WinklerJ.W. ChiangN. Protectins and maresins: Aew pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome.Biochim. Biophys. Acta Mol. Cell Biol. Lipids20151851439741310.1016/j.bbalip.2014.08.00625139562
     [Google Scholar]
  54. BelayevL. MukherjeeP.K. BalaszczukV. CalandriaJ.M. ObenausA. KhoutorovaL. HongS.H. BazanN.G. Neuroprotectin D1 upregulates Iduna expression and provides protection in cellular uncompensated oxidative stress and in experimental ischemic stroke.Cell Death Differ.20172461091109910.1038/cdd.2017.5528430183
     [Google Scholar]
  55. FattoriV. ZaninelliT.H. Rasquel-OliveiraF.S. CasagrandeR. VerriW.A.Jr Specialized pro-resolving lipid mediators: A new class of non-immunosuppressive and non-opioid analgesic drugs.Pharmacol. Res.202015110454910.1016/j.phrs.2019.10454931743775
     [Google Scholar]
  56. LimJ.Y. ParkC.K. HwangS.W. Biological roles of resolvins and related substances in the resolution of pain.BioMed Res. Int.2015201511410.1155/2015/83093026339646
     [Google Scholar]
  57. FangX.X. ZhaiM.N. ZhuM. HeC. WangH. WangJ. ZhangZ.J. Inflammation in pathogenesis of chronic pain: Foe and friend.Mol. Pain2023191744806923117817610.1177/1744806923117817637220667
     [Google Scholar]
  58. SerhanC.N. Pro-resolving lipid mediators are leads for resolution physiology.Nature201451075039210110.1038/nature1347924899309
     [Google Scholar]
  59. SerhanC.N. de la RosaX. JouveneC. Novel mediators and mechanisms in the resolution of infectious inflammation: Evidence for vagus regulation.J. Intern. Med.2019286324025810.1111/joim.1287130565762
     [Google Scholar]
  60. BalasL. RiséP. GandrathD. RovatiG. BolegoC. StellariF. TrentiA. BuccellatiC. DurandT. SalaA. Rapid metabolization of protectin D1 by β-Oxidation of its polar head chain.J. Med. Chem.201962219961997510.1021/acs.jmedchem.9b0146331626541
     [Google Scholar]
  61. LukiwW.J. CuiJ.G. MarcheselliV.L. BodkerM. BotkjaerA. GotlingerK. SerhanC.N. BazanN.G. A role for docosahexaenoic acid-derived neuroprotectin D1 in neural cell survival and Alzheimer disease.J. Clin. Invest.2005115102774278310.1172/JCI2542016151530
     [Google Scholar]
  62. QuL. CaterinaM.J. Accelerating the reversal of inflammatory pain with NPD1 and its receptor GPR37.J. Clin. Invest.201812883246324910.1172/JCI12220330010628
     [Google Scholar]
  63. BangS. XieY.K. ZhangZ.J. WangZ. XuZ.Z. JiR.R. GPR37 regulates macrophage phagocytosis and resolution of inflammatory pain.J. Clin. Invest.201812883568358210.1172/JCI9988830010619
     [Google Scholar]
  64. CahoyJ.D. EmeryB. KaushalA. FooL.C. ZamanianJ.L. ChristophersonK.S. XingY. LubischerJ.L. KriegP.A. KrupenkoS.A. ThompsonW.J. BarresB.A. A transcriptome database for astrocytes, neurons, and oligodendrocytes: A new resource for understanding brain development and function.J. Neurosci.200828126427810.1523/JNEUROSCI.4178‑07.200818171944
     [Google Scholar]
  65. ZhouJ. HeX. DaiW. LiQ. XiangZ. WangY. ZhangT. XuW. WangL. MaoA. GPR37 promotes colorectal cancer against ferroptosis by reprogramming lipid metabolism via p38-SCD1 axis.Apoptosis20242911-121988200110.1007/s10495‑024‑02018‑439306652
     [Google Scholar]
  66. LiangK. GuoZ. ZhangS. ChenD. ZouR. WengY. PengC. XuZ. ZhangJ. LiuX. PangX. JiY. LiaoD. LaiM. PengH. KeY. WangZ. WangY. GPR37 expression as a prognostic marker in gliomas: A bioinformatics-based analysis.Aging (Albany NY)20231519101461016710.18632/aging.20506337837549
     [Google Scholar]
  67. RobertsonK. Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis.bioRxiv202410.1101/2024.04.09.588619
     [Google Scholar]
  68. ChiangN. de la RosaX. LibrerosS. SerhanC.N. Novel resolvin D2 receptor axis in infectious inflammation.J. Immunol.2017198284285110.4049/jimmunol.160165027994074
     [Google Scholar]
  69. HalapinN.A. BazanN.G. NPD1 induction of retinal pigment epithelial cell survival involves PI3K/Akt phosphorylation signaling.Neurochem. Res.201035121944194710.1007/s11064‑010‑0351‑821136150
     [Google Scholar]
  70. MsweliS. PakalaS.B. SyedK. NF-κB transcription factors: Aheir distribution, family expansion, structural conservation, and evolution in animals.Int. J. Mol. Sci.20242518979310.3390/ijms2518979339337282
     [Google Scholar]
  71. MarkusR.P. FernandesP.A. KinkerG.S. da Silveira Cruz-MachadoS. MarçolaM. Immune‐pineal axis – Acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes.Br. J. Pharmacol.2018175163239325010.1111/bph.1408329105727
     [Google Scholar]
  72. MuxelS.M. Pires-LapaM.A. MonteiroA.W.A. CeconE. TamuraE.K. Floeter-WinterL.M. MarkusR.P. NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (AA-NAT) gene.PLoS One2012712e5201010.1371/journal.pone.005201023284853
     [Google Scholar]
  73. ZimmermanS. ReiterR.J. Melatonin and the optics of the human body.Melatonin Res.20192113816010.32794/mr11250016
     [Google Scholar]
  74. AndersonG. Physiological processes underpinning the ubiquitous benefits and interactions of melatonin, butyrate and green tea in neurodegenerative conditions.Melatonin Res.202471204610.32794/mr112500167
     [Google Scholar]
  75. AsatryanA. BazanN. G. Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection.J. Biol. Chem.201729230123901239710.1074/jbc.R117.783076
     [Google Scholar]
  76. SelkoeD.J. HardyJ. The amyloid hypothesis of Alzheimer’s disease at 25 years.EMBO Mol. Med.20168659560810.15252/emmm.20160621027025652
     [Google Scholar]
  77. GlabeC. Intracellular mechanisms of amyloid accumulation and pathogenesis in Alzheimer’s disease.J. Mol. Neurosci.200117213714510.1385/JMN:17:2:13711816787
     [Google Scholar]
  78. OddoS. CaccamoA. ShepherdJ.D. MurphyM.P. GoldeT.E. KayedR. MetherateR. MattsonM.P. AkbariY. LaFerlaF.M. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: Intracellular Abeta and synaptic dysfunction.Neuron200339340942110.1016/S0896‑6273(03)00434‑312895417
     [Google Scholar]
  79. LustbaderJ.W. CirilliM. LinC. XuH.W. TakumaK. WangN. CaspersenC. ChenX. PollakS. ChaneyM. TrincheseF. LiuS. Gunn-MooreF. LueL.F. WalkerD.G. KuppusamyP. ZewierZ.L. ArancioO. SternD. YanS.S. WuH. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease.Science2004304566944845210.1126/science.109123015087549
     [Google Scholar]
  80. DicksonD.W. Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: Cause or effect?J. Clin. Invest.20041141232710.1172/JCI2231715232608
     [Google Scholar]
  81. Bluthe´R.M. DantzerR. KelleyK.W. Effects of interleukin-1 receptor antagonist on the behavioral effects of lipopolysaccharide in rat.Brain Res.1992573231832010.1016/0006‑8993(92)90779‑91387028
     [Google Scholar]
  82. CoriaF. MorenoA. RubioI. GarcíaM.A. MoratoE. JrF.M. The cellular pathology associated with Alzheimer β‐amyloid deposits in non‐demented aged individuals.Neuropathol. Appl. Neurobiol.199319326126810.1111/j.1365‑2990.1993.tb00436.x8355812
     [Google Scholar]
  83. CoriaF. CastañoE. PrelliF. Larrondo-LilloM. van DuinenS. ShelanskiM.L. FrangioneB. Isolation and characterization of amyloid P component from Alzheimer’s disease and other types of cerebral amyloidosis.Lab. Invest.19885844544582965774
     [Google Scholar]
  84. AkbarM. CalderonF. WenZ. KimH.Y. Docosahexaenoic acid: A positive modulator of Akt signaling in neuronal survival.Proc. Natl. Acad. Sci. USA200510231108581086310.1073/pnas.050290310216040805
     [Google Scholar]
  85. BertramL. LillC.M. TanziR.E. The genetics of Alzheimer disease: Back to the future.Neuron201068227028110.1016/j.neuron.2010.10.01320955934
     [Google Scholar]
  86. GoedertM. ClavagueraF. TolnayM. The propagation of prion-like protein inclusions in neurodegenerative diseases.Trends Neurosci.201033731732510.1016/j.tins.2010.04.00320493564
     [Google Scholar]
  87. AkiyamaH. BargerS. BarnumS. BradtB. BauerJ. ColeG.M. CooperN.R. EikelenboomP. EmmerlingM. FiebichB.L. FinchC.E. FrautschyS. GriffinW.S. HampelH. HullM. LandrethG. LueL. MrakR. MackenzieI.R. McGeerP.L. O’BanionM.K. PachterJ. PasinettiG. Plata-SalamanC. RogersJ. RydelR. ShenY. StreitW. StrohmeyerR. TooyomaI. Van MuiswinkelF.L. VeerhuisR. WalkerD. WebsterS. WegrzyniakB. WenkG. Wyss-CorayT. Inflammation and Alzheimer’s disease.Neurobiol. Aging200021338342110.1016/S0197‑4580(00)00124‑X10858586
     [Google Scholar]
  88. Marion-LetellierR. ButlerM. DéchelotteP. PlayfordR.J. GhoshS. Comparison of cytokine modulation by natural peroxisome proliferator–activated receptor γ ligands with synthetic ligands in intestinal-like CaCo-2 cells and human dendritic cells—potential for dietary modulation of peroxisome proliferator–activated receptor γ in intestinal inflammation.Am. J. Clin. Nutr.200887493994810.1093/ajcn/87.4.93918400717
     [Google Scholar]
  89. Luna-MedinaR. Cortes-CanteliM. AlonsoM. SantosA. MartínezA. Perez-CastilloA. Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor γ activation.J. Biol. Chem.200528022214532146210.1074/jbc.M41439020015817469
     [Google Scholar]
  90. ReesD. MilesE.A. BanerjeeT. WellsS.J. RoynetteC.E. WahleK.W.J. CalderP.C. Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: A comparison of young and older men.Am. J. Clin. Nutr.200683233134210.1093/ajcn/83.2.33116469992
     [Google Scholar]
  91. ZhuM. WangX. HjorthE. ColasR.A. SchroederL. GranholmA.C. SerhanC.N. SchultzbergM. Pro-resolving lipid mediators improve neuronal survival and increase Aβ42 phagocytosis.Mol. Neurobiol.20165342733274910.1007/s12035‑015‑9544‑026650044
     [Google Scholar]
  92. SerhanC.N. ChiangN. Van DykeT.E. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators.Nat. Rev. Immunol.20088534936110.1038/nri229418437155
     [Google Scholar]
  93. AritaM. YoshidaM. HongS. TjonahenE. GlickmanJ.N. PetasisN.A. BlumbergR.S. SerhanC.N. Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis.Proc. Natl. Acad. Sci. USA2005102217671767610.1073/pnas.040927110215890784
     [Google Scholar]
  94. McGeerP.L. ItagakiS. TagoH. McGeerE.G. Reactive microglia in patients with senile dementia of the Alzheimer type are positive for the histocompatibility glycoprotein HLA-DR.Neurosci. Lett.1987791-219520010.1016/0304‑3940(87)90696‑33670729
     [Google Scholar]
  95. McGeerP.L. ItagakiS. BoyesB.E. McGeerE.G. Reactive microglia are positive for HLA‐DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains.Neurology19883881285129110.1212/WNL.38.8.12853399080
     [Google Scholar]
  96. JiangH. BurdickD. GlabeC.G. CotmanC.W. TennerA.J. beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain.J. Immunol.1994152105050505910.4049/jimmunol.152.10.50508176223
     [Google Scholar]
  97. VeerhuisR. JanssenI. De GrootC.J.A. Van MuiswinkelF.L. HackC.E. EikelenboomP. Cytokines associated with amyloid plaques in Alzheimer’s disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor.Exp. Neurol.1999160128929910.1006/exnr.1999.719910630213
     [Google Scholar]
  98. HagaS. AizawaT. IshiiT. IkedaK. Complement gene expression in mouse microglia and astrocytes in culture: Comparisons with mouse peritoneal macrophages.Neurosci. Lett.1996216319119410.1016/0304‑3940(96)13040‑88897490
     [Google Scholar]
  99. WalkerD.G. Expression and regulation of complement C1q by human THP-1-derived macrophages.Mol. Chem. Neuropathol.1998342-319721810.1007/BF0281508010327418
     [Google Scholar]
  100. GasqueP. ChanP. FontaineM. IschenkoA. LamaczM. GötzeO. MorganB.P. Identification and characterization of the complement C5a anaphylatoxin receptor on human astrocytes.J. Immunol.1995155104882488910.4049/jimmunol.155.10.48827594492
     [Google Scholar]
  101. GoldgaberD. HarrisH.W. HlaT. MaciagT. DonnellyR.J. JacobsenJ.S. VitekM.P. GajdusekD.C. Interleukin 1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells.Proc. Natl. Acad. Sci. USA198986197606761010.1073/pnas.86.19.76062508093
     [Google Scholar]
  102. DebS. GottschallP.E. Increased production of matrix metalloproteinases in enriched astrocyte and mixed hippocampal cultures treated with beta-amyloid peptides.J. Neurochem.19966641641164710.1046/j.1471‑4159.1996.66041641.x8627321
     [Google Scholar]
  103. LouisJ.C. MagalE. TakayamaS. VaronS. CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death.Science1993259509568969210.1126/science.84303208430320
     [Google Scholar]
  104. McKeeA.C. KawallN.W. SchumacherJ.S. BealM.F. The neurotoxicity of amyloid beta protein in aged primates.Amyloid1998511910.3109/135061298090072839546999
     [Google Scholar]
  105. AntelJ.P. BecherB. OwensT. Immunotherapy for multiple sclerosis: From theory to practice.Nat. Med.19962101074107510.1038/nm1096‑10748837599
     [Google Scholar]
  106. GoodP.F. WernerP. HsuA. OlanowC.W. PerlD.P. Evidence of neuronal oxidative damage in Alzheimer’s disease.Am. J. Pathol.1996149121288686745
     [Google Scholar]
  107. MogiM. HaradaM. RiedererP. NarabayashiH. FujitaK. NagatsuT. Tumor necrosis factor-α (TNF-α) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients.Neurosci. Lett.19941651-220821010.1016/0304‑3940(94)90746‑38015728
     [Google Scholar]
  108. MarkesberyW.R. CarneyJ.M. Oxidative alterations in Alzheimer’s disease.Brain Pathol.19999113314610.1111/j.1750‑3639.1999.tb00215.x9989456
     [Google Scholar]
  109. SuJ.H. DengG. CotmanC.W. Neuronal DNA damage precedes tangle formation and is associated with up-regulation of nitrotyrosine in Alzheimer’s disease brain.Brain Res.19977741-219319910.1016/S0006‑8993(97)81703‑99452208
     [Google Scholar]
  110. Van MuiswinkelF.L. RauppS.F.A. de VosN.M. SmitsH.A. VerhoefJ. EikelenboomP. NottetH.S.L.M. The amino-terminus of the amyloid-β protein is critical for the cellular binding and consequent activation of the respiratory burst of human macrophages.J. Neuroimmunol.199996112113010.1016/S0165‑5728(99)00019‑310227431
     [Google Scholar]
  111. ChaoC.C. HuS. ShengW.S. BuD. BukrinskyM.I. PetersonP.K. Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism.Glia199616327628410.1002/(SICI)1098‑1136(199603)16:3<276::AID‑GLIA10>3.0.CO;2‑X8833198
     [Google Scholar]
  112. LeeS.C. DicksonD.W. LiuW. BrosnanC.F. Induction of nitric oxide synthase activity in human astrocytes by interleukin-1β and interferon-γ.J. Neuroimmunol.1993461-2192410.1016/0165‑5728(93)90229‑R7689587
     [Google Scholar]
  113. ReynoldsW.F. RheesJ. MaciejewskiD. PaladinoT. SieburgH. MakiR.A. MasliahE. Myeloperoxidase polymorphism is associated with gender specific risk for Alzheimer’s disease.Exp. Neurol.19991551314110.1006/exnr.1998.69779918702
     [Google Scholar]
  114. ChenP. VãricelE. LagardeM. GuichardantM. Poxytrins, a class of oxygenated products from polyunsaturated fatty acids, potently inhibit blood platelet aggregation.FASEB J.201125138238810.1096/fj.10‑16183620833872
     [Google Scholar]
  115. NesmanJ.I. Gangestad PrimdahlK. TungenJ.E. PalmasF. DalliJ. HansenT.V. Synthesis, structural confirmation, and biosynthesis of 22-OH-PD1n-3 DPA.Molecules20192418322810.3390/molecules2418322831491851
     [Google Scholar]
  116. NesmanJ.I. ChenO. LuoX. JiR.R. SerhanC.N. HansenT.V. A new synthetic protectin D1 analog 3-oxa-PD1 n-3 DPA reduces neuropathic pain and chronic itch in mice.Org. Biomol. Chem.202119122744275210.1039/D0OB02136A33687402
     [Google Scholar]
  117. TungenJ.E. AursnesM. RamonS. ColasR.A. SerhanC.N. OlbergD.E. NuruddinS. WillochF. HansenT.V. Synthesis of protectin D1 analogs: Novel pro-resolution and radiotracer agents.Org. Biomol. Chem.201816366818682310.1039/C8OB01232F30204204
     [Google Scholar]
  118. BalasL. DurandT. Dihydroxylated E,E,Z-docosatrienes. An overview of their synthesis and biological significance.Prog. Lipid Res.20166111810.1016/j.plipres.2015.10.00226545300
     [Google Scholar]
  119. DayakerG. DurandT. BalasL. A versatile and stereocontrolled total synthesis of dihydroxylated docosatrienes containing a conjugated E,E,Z-triene.Chemistry201420102879288710.1002/chem.20130452624520010
     [Google Scholar]
  120. LiuM. BoussettaT. Makni-MaalejK. FayM. DrissF. El-BennaJ. LagardeM. GuichardantM. Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities.Lipids2014491495710.1007/s11745‑013‑3863‑624254970
     [Google Scholar]
  121. HamidzadehK. WestcottJ. WourmsN. ShayA.E. PanigrahyA. MartinM.J. NshimiyimanaR. SerhanC.N. A newly synthesized 17-epi-NeuroProtectin D1/17-epi-Protectin D1: Authentication and functional regulation of inflammation-resolution.Biochem. Pharmacol.202220311518110.1016/j.bcp.2022.11518135850309
     [Google Scholar]
/content/journals/cn/10.2174/011570159X365720250225080257
Loading
The Multifaceted Role of Neuroprotectin D1: Physiological, Pathophysiological, and Pharmacological Insights in Neurodegenerative Diseases
Curr. Neuropharmacol. 23, 1215 (2025); https://doi.org/10.2174/011570159X365720250225080257
/content/journals/cn/10.2174/011570159X365720250225080257
/content/journals/cn/10.2174/011570159X365720250225080257
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Cyclooxygenases; docosahexaenoic acid; inflammatory cytokines; lipoxygenases; neurodegenerative diseases; Neuroprotectin D1; neuroprotective; pro-resolving lipid mediators; protectin D

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