Plasmalogen as a Bioactive Lipid Drug: From Preclinical Research Challenges to Opportunities in Nanomedicine

. 2025 Aug ; 7 (8) : e70028. [epub] 20250604

Status PubMed-not-MEDLINE Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/pmid40746866

Plasmalogens are natural glycerophospholipids that account for approximately 15%-20% (mol%) of human tissues' cellular membrane phospholipid composition. They play an important role in lipid membrane organization and function, including acting as endogenous antioxidants. Plasmalogens contain a vinyl-ether linked alkyl chain at position sn-1, characteristic of vinyl-ether lipids, and often a polyunsaturated fatty acid (PUFA) acyl chain at position sn-2 of the glycerol backbone. The role of plasmalogens in various patho-physiological processes has been revealed in recent years, including various neurological disorders associated with plasmalogen deficiency. Plasmalogen Replacement Therapy (PRT) is a therapeutic approach that aims to increase plasmalogen levels in the body and address plasmalogen deficiencies in diseases such as age-related neurodegenerative diseases, cardiovascular diseases, certain genetic peroxisomal disorders, and metabolic disorders. We provide a detailed overview of current information on the role of plasmalogens in health and disease. We summarize various strategies for regulating plasmalogen levels and highlight recent advancements in therapeutic applications. We also focus on the potential application of nanomedicine for treating disorders associated with PUFA-lipid and plasmalogen deficiencies.

Zobrazit více v PubMed

Küllenberg D., Taylor L. A., Schneider M., and Massing U., “Health Effects of Dietary Phospholipids,” Lipids in Health and Disease 11 (2012): 3. PubMed PMC

Sastry P. S., “Lipids of Nervous Tissue: Composition and Metabolism,” Progress in Lipid Research 24 (1985): 69–176. PubMed

Ziegler A. B. and Tavosanis G., “Glycerophospholipids—Emerging Players in Neuronal Dendrite Branching and Outgrowth,” Developmental Biology 451 (2019): 25–34. PubMed

Dietschy J. M. and Turley S. D., “Cholesterol Metabolism in the Brain,” Current Opinion in Lipidology 12 (2001): 105–112. PubMed

Tapiero H., Nguyen Ba G., Couvreur P., and Tew K. D., “Polyunsaturated Fatty Acids (PUFA) and Eicosanoids in Human Health and Pathologies,” Biomedicine & Pharmacotherapy 56 (2002): 215–222. PubMed

Fontaine D., Figiel S., Félix R., et al., “Roles of Endogenous Ether Lipids and Associated PUFAs in the Regulation of Ion Channels and Their Relevance for Disease,” Journal of Lipid Research 61 (2020): 840–858. PubMed PMC

Ecker J. and Liebisch G., “Application of Stable Isotopes to Investigate the Metabolism of Fatty Acids, Glycerophospholipid and Sphingolipid Species,” Progress in Lipid Research 54 (2014): 14–31. PubMed

Jiménez‐Rojo N. and Riezman H., “On the Road to Unraveling the Molecular Functions of Ether Lipids,” FEBS Letters 593 (2019): 2378–2389. PubMed

Dean J. M. and Lodhi I. J., “Structural and Functional Roles of Ether Lipids,” Protein & Cell 9 (2018): 196–206. PubMed PMC

Lohner K., “Is the High Propensity of Ethanolamine Plasmalogens to Form Non‐Lamellar Lipid Structures Manifested in the Properties of Biomembranes?,” Chemistry and Physics of Lipids 81 (1996): 167–184. PubMed

Farooqui A. A. and Horrocks L. A., “Plasmalogens: Workhorse Lipids of Membranes in Normal and Injured Neurons and Glia,” Neuroscientist 7 (2001): 232–245. PubMed

Panganamala R. V., Horrocks L. A., Geer J. C., and Cornwell D. G., “Positions of Double Bonds in the Monounsaturated Alk‐1‐Enyl Groups From the Plasmalogens of Human Heart and Brain,” Chemistry and Physics of Lipids 6 (1971): 97–102. PubMed

Braverman N. E. and Moser A. B., “Functions of Plasmalogen Lipids in Health and Disease,” Biochimica et Biophysica Acta 1822 (2012): 1442–1452. PubMed

Dorninger F., Werner E. R., Berger J., and Watschinger K., “Regulation of Plasmalogen Metabolism and Traffic in Mammals: The Fog Begins to Lift,” Frontiers in Cell and Developmental Biology 10 (2022): 946393. PubMed PMC

Papin M., Bouchet A. M., Chantôme A., and Vandier C., “Ether‐Lipids and Cellular Signaling: A Differential Role of Alkyl‐ and Alkenyl‐Ether‐Lipids?,” Biochimie 215 (2023): 50–59. PubMed

Simbari F., McCaskill J., Coakley G., et al., “Plasmalogen Enrichment in Exosomes Secreted by a Nematode Parasite Versus Those Derived From Its Mouse Host: Implications for Exosome Stability and Biology,” Journal of Extracellular Vesicles 5 (2016): 30741. PubMed PMC

Hossain M. S., Mawatar S., and Fujino T., “Biological Functions of Plasmalogens,” in Peroxisome Biology: Experimental Models, Peroxisomal Disorders and Neurological Diseases. Advances in Experimental Medicine and Biology, vol. 1299, ed. Lizard G. (Springer, 2020), 171–193, 10.1007/978-3-030-60204-8_13. PubMed DOI

Fhaner C. J., Liu S., Zhou X., and Reid G. E., “Functional Group Selective Derivatization and Gas‐Phase Fragmentation Reactions of Plasmalogen Glycerophospholipids,” Mass Spectrom (Tokyo) 2, no. Spec Iss (2013): S0015. PubMed PMC

Honsho M., Tanaka M., Zoeller R. A., and Fujiki Y., “Distinct Functions of Acyl/Alkyl Dihydroxyacetonephosphate Reductase in Peroxisomes and Endoplasmic Reticulum,” Frontiers in Cell and Developmental Biology 8 (2020): 855. PubMed PMC

Kraffe E., Soudant P., and Marty Y., “Fatty Acids of Serine, Ethanolamine, and Choline Plasmalogens in Some Marine Bivalves,” Lipids 39 (2004): 59–66. PubMed

Chong K., Almsherqi Z. A., Zhuo R., and Deng Y., “Plasmalogen‐Rich Foods Promote the Formation of Cubic Membranes in Amoeba Chaos Under Stress Conditions,” FEBS Open Bio 11 (2021): 2319–2328. PubMed PMC

Jahn R., Lang T., and Südhof T. C., “Membrane Fusion,” Cell 112 (2003): 519–533. PubMed

Roos D. S. and Choppin P. W., “Biochemical Studies on Cell Fusion. I. Lipid Composition of Fusion‐Resistant Cells,” Journal of Cell Biology 101 (1985): 1578–1590. PubMed PMC

Rubio J. M., Astudillo A. M., Casas J., Balboa M. A., and Balsinde J., “Regulation of Phagocytosis in Macrophages by Membrane Ethanolamine Plasmalogens,” Frontiers in Immunology 9 (2018): 1723. PubMed PMC

Gu J., Chen L., Sun R., et al., “Plasmalogens Eliminate Aging‐Associated Synaptic Defects and Microglia‐Mediated Neuroinflammation in Mice,” Frontiers in Molecular Biosciences 9 (2022): 815320. PubMed PMC

Farooqui A. A., Rapoport S. I., and Horrocks L. A., “Membrane Phospholipid Alterations in Alzheimer's Disease: Deficiency of Ethanolamine Plasmalogens,” Neurochemical Research 22, no. 4 (1997): 523–527. PubMed

Bayir H., Anthonymuthu T. S., Tyurina Y. Y., et al., “Achieving Life Through Death: Redox Biology of Lipid Peroxidation in Ferroptosis,” Cell Chemical Biology 27 (2020): 387–408. PubMed PMC

Brosche T., “Plasmalogen Phospholipids—Facts and Theses to Their Antioxidative Qualities,” Archives of Gerontology and Geriatrics 25 (1997): 73–81. PubMed

Spiteller G., “Peroxyl Radicals: Inductors of Neurodegenerative and Other Inflammatory Diseases. Their Origin and How They Transform Cholesterol, Phospholipids, Plasmalogens, Polyunsaturated Fatty Acids, Sugars, and Proteins Into Deleterious Products,” Free Radical Biology and Medicine 41 (2006): 362–387. PubMed

Zoeller R. A., Lake A. C., Nagan N., Gaposchkin D. P., Legner M. A., and Lieberthal W., “Plasmalogens as Endogenous Antioxidants: Somatic Cell Mutants Reveal the Importance of the Vinyl Ether,” Biochemical Journal 338 (1999): 769–776. PubMed PMC

Tremblay M.‐È., Almsherqi Z. A., and Deng Y., “Plasmalogens and Platelet‐Activating Factor Roles in Chronic Inflammatory Diseases,” BioFactors 48 (2022): 1203–1216. PubMed

Nathan C. and Ding A., “Nonresolving Inflammation,” Cell 140 (2010): 871–882. PubMed

Bozelli J. C., Azher S., and Epand R. M., “Plasmalogens and Chronic Inflammatory Diseases,” Frontiers in Physiology 12 (2021): 730829. PubMed PMC

Rong P., Wang J.‐L., Angelova A., Almsherqi Z. A., and Deng Y., “Plasmalogenic Lipid Analogs as Platelet‐Activating Factor Antagonists: A Potential Novel Class of Anti‐Inflammatory Compounds,” Frontiers in Cell and Developmental Biology 10 (2022): 859421. PubMed PMC

Sejimo S., Hossain M. S., and Akashi K., “Scallop‐Derived Plasmalogens Attenuate the Activation of PKCδ Associated With the Brain Inflammation,” Biochemical and Biophysical Research Communications 503 (2018): 837–842. PubMed

Fuchs B., Süβ R., and Schiller J., “An Update of MALDI‐TOF Mass Spectrometry in Lipid Research,” Progress in Lipid Research 49 (2010): 450–475. PubMed

Yamashita S., Honjo A., Aruga M., Nakagawa K., and Miyazawa T., “Preparation of Marine Plasmalogen and Selective Identification of Molecular Species by LC‐MS/MS,” Journal of Oleo Science 63 (2014): 423–430. PubMed

Fuchs B., “Analytical Methods for (Oxidized) Plasmalogens: Methodological Aspects and Applications,” Free Radical Research 49 (2015): 599–617. PubMed

Hu C., Wang M., and Han X., “Shotgun Lipidomics in Substantiating Lipid Peroxidation in Redox Biology: Methods and Applications,” Redox Biology 12 (2017): 946–955. PubMed PMC

Maeba R., Maeda T., Kinoshita M., et al., “Plasmalogens in Human Serum Positively Correlate With High‐Density Lipoprotein and Decrease With Aging,” Journal of Atherosclerosis and Thrombosis 14 (2007): 12–18. PubMed

Goldfine H., “The Appearance, Disappearance and Reappearance of Plasmalogens in Evolution,” Progress in Lipid Research 49 (2010): 493–498. PubMed

Malheiro A. R., da Silva T. F., and Brites P., “Plasmalogens and Fatty Alcohols in Rhizomelic Chondrodysplasia Punctata and Sjögren‐Larsson Syndrome,” Journal of Inherited Metabolic Disease 38 (2015): 111–121. PubMed

Dragonas C., Bertsch T., Sieber C. C., and Brosche T., “Plasmalogens as a Marker of Elevated Systemic Oxidative Stress in Parkinson's Disease,” Clinical Chemistry and Laboratory Medicine 47, no. 7 (2009): 894–897. PubMed

Grimm M. O. W., Grösgen S., Riemenschneider M., Tanila H., Grimm H. S., and Hartmann T., “From Brain to Food: Analysis of Phosphatidylcholins, Lyso‐Phosphatidylcholins and Phosphatidylcholin‐Plasmalogens Derivates in Alzheimer's Disease Human Post Mortem Brains and Mice Model via Mass Spectrometry,” Journal of Chromatography A 1218 (2011): 7713–7722. PubMed

Goodenowe D. B., Cook L. L., Liu J., et al., “Peripheral Ethanolamine Plasmalogen Deficiency: A Logical Causative Factor in Alzheimer's Disease and Dementia,” Journal of Lipid Research 48 (2007): 2485–2498. PubMed

J. C. Bozelli, Jr. and Epand R. M., “Plasmalogen Replacement Therapy,” Membranes 11, no. 11 (2021): 838. PubMed PMC

Werner E. R., Keller M. A., Sailer S., et al., “The TMEM189 Gene Encodes Plasmanylethanolamine Desaturase Which Introduces the Characteristic Vinyl Ether Double Bond Into Plasmalogens,” Proceedings of the National Academy of Sciences of the USA 117 (2020): 7792–7798. PubMed PMC

Horibata Y. and Sugimoto H., “Differential Contributions of Choline Phosphotransferases CPT1 and CEPT1 to the Biosynthesis of Choline Phospholipids,” Journal of Lipid Research 62 (2021): 100100. PubMed PMC

Horibata Y., Elpeleg O., Eran A., et al., “EPT1 (Selenoprotein I) is Critical for the Neural Development and Maintenance of Plasmalogen in Humans,” Journal of Lipid Research 59 (2018): 1015–1026. PubMed PMC

Lodhi I. J., Yin L., Jensen‐Urstad A. P. L., et al., “Inhibiting Adipose Tissue Lipogenesis Reprograms Thermogenesis and PPARγ Activation to Decrease Diet‐Induced Obesity,” Cell Metabolism 16 (2012): 189–201. PubMed PMC

Honsho M., Asaoku S., and Fujiki Y., “Posttranslational Regulation of Fatty Acyl‐CoA Reductase 1, Far1, Controls Ether Glycerophospholipid Synthesis,” Journal of Biological Chemistry 285, no. 12 (2010): 8537–8542. PubMed PMC

Honsho M., Asaoku S., Fukumoto K., and Fujiki Y., “Topogenesis and Homeostasis of Fatty Acyl‐CoA Reductase 1,” Journal of Biological Chemistry 288 (2013): 34588–34598. PubMed PMC

Mangold H. K. and Weber N., “Biosynthesis and Biotransformation of Ether Lipids,” Lipids 22 (1987): 789–799. PubMed

Honsho M., Asaoku S., and Fujiki Y., “Posttranslational Regulation of Fatty Acyl‐CoA Reductase 1, Far1, Controls Ether Glycerophospholipid Synthesis,” Journal of Biological Chemistry 285 (2010): 8537–8542. PubMed PMC

Molendi‐Coste O., Legry V., and Leclercq I. A., “Why and How Meet n‐3 PUFA Dietary Recommendations?,” Gastroenterology Research and Practice 2011 (2010): e364040. PubMed PMC

Rittenhouse‐Simmons S., Russell F. A., and Deykin D., “Transfer of Arachidonic Acid to Human Platelet Plasmalogen in Response to Thrombin,” Biochemical and Biophysical Research Communications 70 (1976): 295–301. PubMed

Gaposchkin D. P., Farber H. W., and Zoeller R. A., “On the Importance of Plasmalogen Status in Stimulated Arachidonic Acid Release in the Macrophage Cell Line RAW 264.7,” Biochimica et Biophysica Acta 1781 (2008): 213–219. PubMed

Dorninger F., Brodde A., Braverman N. E., et al., “Homeostasis of Phospholipids—The Level of Phosphatidylethanolamine Tightly Adapts to Changes in Ethanolamine Plasmalogens,” Biochimica et Biophysica Acta 1851 (2015): 117–128. PubMed PMC

Fu S.‐S., Wen M., Zhao Y.‐C., et al., “Short‐Term Supplementation of EPA‐Enriched Ethanolamine Plasmalogen Increases the Level of DHA in the Brain and Liver of n‐3 PUFA Deficient Mice in Early Life After Weaning,” Food & Function 13 (2022): 1906–1920. PubMed

Kagan V. E., Mao G., Qu F., et al., “Oxidized Arachidonic and Adrenic PEs Navigate Cells to Ferroptosis,” Nature Chemical Biology 13 (2017): 81–90. PubMed PMC

Chen X., Kang R., Kroemer G., and Tang D., “Organelle‐Specific Regulation of Ferroptosis,” Cell Death and Differentiation 28 (2021): 2843–2856. PubMed PMC

Wang G. and Wang T., “The Role of Plasmalogen in the Oxidative Stability of Neutral Lipids and Phospholipids,” Journal of Agricultural and Food Chemistry 58 (2010): 2554–2561. PubMed

Li J., Cao F., Yin H., et al., “Ferroptosis: Past, Present and Future,” Cell Death & Disease 11 (2020): 1–13. PubMed PMC

Morand O. H., Zoeller R. A., and Raetz C. R., “Disappearance of Plasmalogens From Membranes of Animal Cells Subjected to Photosensitized Oxidation,” Journal of Biological Chemistry 263 (1988): 11597–11606. PubMed

Jenkins C. M., Yang K., Liu G., Moon S. H., Dilthey B. G., and Gross R. W., “Cytochrome c Is an Oxidative Stress‐Activated Plasmalogenase That Cleaves Plasmenylcholine and Plasmenylethanolamine at the Sn‐1 Vinyl Ether Linkage,” Journal of Biological Chemistry 293 (2018): 8693–8709. PubMed PMC

Weisser M., Vieth M., Stolte M., et al., “Dramatic Increase of a‐Hydroxyaldehydes Derived From Plasmalogens in the Aged Human Brain,” Chemistry and Physics of Lipids 90, no. 1–2 (1997): 135–142. PubMed

Che H., Zhang L., Ding L., et al., “EPA‐Enriched Ethanolamine Plasmalogen and EPA‐Enriched Phosphatidylethanolamine Enhance BDNF/TrkB/CREB Signaling and Inhibit Neuronal Apoptosis In Vitro and In Vivo,” Food & Function 11 (2020): 1729–1739. PubMed

Hoxhaj G. and Manning B. D., “The PI3K‐AKT Network at the Interface of Oncogenic Signalling and Cancer Metabolism,” Nature Reviews. Cancer 20 (2020): 74–88. PubMed PMC

Hossain M. S., Ifuku M., Take S., Kawamura J., Miake K., and Katafuchi T., “Plasmalogens Rescue Neuronal Cell Death Through an Activation of AKT and ERK Survival Signaling,” PLoS One 8 (2013): e83508. PubMed PMC

Hossain M. S., Mineno K., and Katafuchi T., “Neuronal Orphan G‐Protein Coupled Receptor Proteins Mediate Plasmalogens‐Induced Activation of ERK and Akt Signaling,” PLoS One 11 (2016): e0150846. PubMed PMC

da Silva T. F., Eira J., Lopes A. T., et al., “Peripheral Nervous System Plasmalogens Regulate Schwann Cell Differentiation and Myelination,” Journal of Clinical Investigation 124 (2014): 2560–2570. PubMed PMC

Azad A. K., Sheikh A. M., Haque M. A., et al., “Time‐Dependent Analysis of Plasmalogens in the Hippocampus of an Alzheimer's Disease Mouse Model: A Role of Ethanolamine Plasmalogen,” Brain Sciences 11 (2021): 1603. PubMed PMC

Guan Z., Wang Y., Cairns N. J., Lantos P. L., Dallner G., and Sindelar P. J., “Decrease and Structural Modifications of Phosphatidylethanolamine Plasmalogen in the Brain With Alzheimer Disease,” Journal of Neuropathology & Experimental Neurology 58 (1999): 740–747. PubMed

Han X., Holtzman D. M., and D. W. McKeel, Jr. , “Plasmalogen Deficiency in Early Alzheimer's Disease Subjects and in Animal Models: Molecular Characterization Using Electrospray Ionization Mass Spectrometry,” Journal of Neurochemistry 77 (2001): 1168–1180. PubMed

Benjamin D. I., Cozzo A., Ji X., et al., “Ether Lipid Generating Enzyme AGPS Alters the Balance of Structural and Signaling Lipids to Fuel Cancer Pathogenicity,” Proceedings of the National Academy of Sciences of the USA 110 (2013): 14912–14917. PubMed PMC

Naffaa V., Magny R., Regazzetti A., et al., “Shift in Phospholipid and Fatty Acid Contents Accompanies Brain Myelination,” Biochimie 203 (2022): 20–31. PubMed

Malheiro A. R., Correia B., Ferreira da Silva T., Bessa‐Neto D., Van Veldhoven P. P., and Brites P., “Leukodystrophy Caused by Plasmalogen Deficiency Rescued by Glyceryl 1‐Myristyl Ether Treatment,” Brain Pathology 29 (2019): 622–639. PubMed PMC

Jang J. E., Park H., Yoo H. J., et al., “Protective Role of Endogenous Plasmalogens Against Hepatic Steatosis and Steatohepatitis in Mice,” Hepatology 66 (2017): 416–431. PubMed PMC

Honsho M., Dorninger F., Abe Y., et al., “Impaired Plasmalogen Synthesis Dysregulates Liver X Receptor‐Dependent Transcription in Cerebellum,” Journal of Biochemistry 166 (2019): 353–361. PubMed

Nguma E., Yamashita S., Kumagai K., et al., “Ethanolamine Plasmalogen Suppresses Apoptosis in Human Intestinal Tract Cells In Vitro by Attenuating Induced Inflammatory Stress,” ACS Omega 6 (2021): 3140–3148. PubMed PMC

Ali F., Hossain M. S., Sejimo S., and Akashi K., “Plasmalogens Inhibit Endocytosis of Toll‐Like Receptor 4 to Attenuate the Inflammatory Signal in Microglial Cells,” Molecular Neurobiology 56 (2019): 3404–3419. PubMed

Hossain M. S., Mawatari S., and Fujino T., “Plasmalogens Inhibit Neuroinflammation and Promote Cognitive Function,” Brain Research Bulletin 192 (2023): 56–61. PubMed

Hossain M. S., Abe Y., Ali F., et al., “Reduction of Ether‐Type Glycerophospholipids, Plasmalogens, by NF‐kB Signal Leading to Microglial Activation,” Journal of Neuroscience 37 (2017): 4074–4092. PubMed PMC

Ginsberg L., Rafique S., Xuereb J. H., Rapoport S. I., and Gershfeld N. L., “Disease and Anatomic Specificity of Ethanolamine Plasmalogen Deficiency in Alzheimer's Disease Brain,” Brain Research 698 (1995): 223–226. PubMed

Chan R. B., Oliveira T. G., Cortes E. P., et al., “Comparative Lipidomic Analysis of Mouse and Human Brain With Alzheimer Disease,” Journal of Biological Chemistry 287 (2012): 2678–2688. PubMed PMC

Pradas I., Jové M., Huynh K., et al., “Exceptional Human Longevity Is Associated With a Specific Plasma Phenotype of Ether Lipids,” Redox Biology 21 (2019): 101127. PubMed PMC

André A., Juanéda P., Sébédio J. L., and Chardigny J. M., “Plasmalogen Metabolism‐Related Enzymes in Rat Brain During Aging: Influence of n‐3 Fatty Acid Intake,” Biochimie 88 (2006): 103–111. PubMed

Bams‐Mengerink A. M., Koelman J. H., Waterham H., Barth P. G., and Poll‐The B. T., “The Neurology of Rhizomelic Chondrodysplasia Punctata,” Orphanet Journal of Rare Diseases 8 (2013): 174. PubMed PMC

Motley A. M., Hettema E. H., Hogenhout E. M., et al., “Rhizomelic Chondrodysplasia Punctata Is a Peroxisomal Protein Targeting Disease Caused by a Non‐Functional PTS2 Receptor,” Nature Genetics 15 (1997): 377–380. PubMed

Braverman N., Chen L., Lin P., et al., “Mutation Analysis ofPEX7 in 60 Probands With Rhizomelic Chondrodysplasia Punctata and Functional Correlations of Genotype With Phenotype,” Human Mutation 20 (2002): 284–297. PubMed

Alkan A., Kutlu R., Yakinci C., Sigirci A., Aslan M., and Sarac K., “Delayed Myelination in a Rhizomelic Chondrodysplasia Punctata Case: MR Spectroscopy Findings,” Magnetic Resonance Imaging 21 (2003): 77–80. PubMed

Brites P., Motley A. M., Gressens P., et al., “Impaired Neuronal Migration and Endochondral Ossification in Pex7 Knockout Mice: A Model for Rhizomelic Chondrodysplasia Punctata,” Human Molecular Genetics 12 (2003): 2255–2267. PubMed

Braverman N., Zhang R., Chen L., et al., “A Pex7 Hypomorphic Mouse Model for Plasmalogen Deficiency Affecting the Lens and Skeleton,” Molecular Genetics and Metabolism 99 (2010): 408–416. PubMed PMC

Rodemer C., Thai T.‐P., Brugger B., et al., “Inactivation of Ether Lipid Biosynthesis Causes Male Infertility, Defects in Eye Development and Optic Nerve Hypoplasia in Mice,” Human Molecular Genetics 12 (2003): 1881–1895. PubMed

Liegel R., Chang B., Dubielzig R., and Sidjanin D. J., “Blind Sterile 2 (bs2), a Hypomorphic Mutation in Agps, Results in Cataracts and Male Sterility in Mice,” Molecular Genetics and Metabolism 103 (2011): 51–59. PubMed PMC

Komljenovic D., Sandhoff R., Teigler A., Heid H., Just W. W., and Gorgas K., “Disruption of Blood‐Testis Barrier Dynamics in Ether‐Lipid‐Deficient Mice,” Cell and Tissue Research 337 (2009): 281–299. PubMed

Brites P., Mooyer P. A. W., el Mrabet L., Waterham H. R., and Wanders R. J. A., “Plasmalogens Participate in Very‐Long‐Chain Fatty Acid‐Induced Pathology,” Brain 132 (2009): 482–492. PubMed

Yamashita S., Kiko T., Fujiwara H., et al., “Alterations in the Levels of Amyloid‐β, Phospholipid Hydroperoxide, and Plasmalogen in the Blood of Patients With Alzheimer's Disease: Possible Interactions Between Amyloid‐β and These Lipids,” Journal of Alzeimers Disease 50 (2016): 527–537. PubMed

Otoki Y., Kato S., Nakagawa K., et al., “Lipidomic Analysis of Postmortem Prefrontal Cortex Phospholipids Reveals Changes in Choline Plasmalogen Containing Docosahexaenoic Acid and Stearic Acid Between Cases With and Without Alzheimer's Disease,” Neuromolecular Medicine 23 (2021): 161–175. PubMed

Goodenowe D. B. and Senanayake V., “Relation of Serum Plasmalogens and APOE Genotype to Cognition and Dementia in Older Persons in a Cross‐Sectional Study,” Brain Sciences 9 (2019): 92. PubMed PMC

Wood P. L., Mankidy R., Ritchie S., et al., “Circulating Plasmalogen Levels and Alzheimer Disease Assessment Scale‐Cognitive Scores in Alzheimer Patients,” Journal of Psychiatry and Neuroscience 35 (2010): 59–62. PubMed PMC

Mawatari S., Fukata M., Arita T., Maruyama T., Kono S., and Fujino T., “Decreases of Ethanolamine Plasmalogen and Phosphatidylcholine in Erythrocyte Are a Common Phenomenon in Alzheimer's, Parkinson's, and Coronary Artery Diseases,” Brain Research Bulletin 189 (2022): 5–10. PubMed

Fujino T., “Effects of Plasmalogen on Patients With Moderate‐To‐Severe Alzheimer's Disease and Blood Plasmalogen Changes: A Multi‐Center, Open‐Label Study,” Journal of Alzheimers Disease and Parkinsonism 9 (2019): 474.

Kling M. A., Goodenowe D. B., Senanayake V., et al., “Circulating Ethanolamine Plasmalogen Indices in Alzheimer's Disease: Relation to Diagnosis, Cognition, and CSF Tau,” Alzheimer's & Dementia 16 (2020): 1234–1247. PubMed PMC

Kou J., Kovacs G. G., Höftberger R., et al., “Peroxisomal Alterations in Alzheimer's Disease,” Acta Neuropathologica 122 (2011): 271–283. PubMed PMC

Maeba R., Araki A., and Fujiwara Y., “Chapter Three—Serum Ethanolamine Plasmalogen and Urine Myo‐Inositol as Cognitive Decline Markers,” in Advances in Clinical Chemistry, vol. 87 (Elsevier Inc., 2018), 69–111, 10.1016/bs.acc.2018.08.001. PubMed DOI

Calvano C. D., Ventura G., Sardanelli A. M. M., et al., “Searching for Potential Lipid Biomarkers of Parkinson's Disease in Parkin‐Mutant Human Skin Fibroblasts by HILIC‐ESI‐MS/MS: Preliminary Findings,” International Journal of Molecular Sciences 20 (2019): 3341. PubMed PMC

Fabelo N., Martín V., Santpere G., et al., “Severe Alterations in Lipid Composition of Frontal Cortex Lipid Rafts From Parkinson's Disease and Incidental Parkinson's Disease,” Molecular Medicine 17 (2011): 1107–1118. PubMed PMC

Aubourg P. and Wanders R., “Chapter 163 ‐ Peroxisomal Disorders,” in Handbook of Clinical Neurology, ed. Dulac O., Lassonde M., and Sarnat H. B. (Elsevier, 2013), 1593–1609, https://www.sciencedirect.com/science/article/pii/B9780444595652000289. PubMed

Rothhaar T. L., Grösgen S., Haupenthal V. J., et al., “Plasmalogens Inhibit APP Processing by Directly Affecting γ‐Secretase Activity in Alzheimer's Disease,” Scientific World Journal 2012 (2012): 1–15. PubMed PMC

Yamashita S., Kanno S., Nakagawa K., Kinoshita M., and Miyazawa T., “Extrinsic Plasmalogens Suppress Neuronal Apoptosis in Mouse Neuroblastoma Neuro‐2A Cells: Importance of Plasmalogen Molecular Species,” RSC Advances 5 (2015): 61012–61020.

Wu Y., Angelov B., Deng Y., et al., “Sustained CREB Phosphorylation by Lipid‐Peptide Liquid Crystalline Nanoassemblies,” Communications Chemistry 6 (2023): 1–16. PubMed PMC

Yamashita S., Hashimoto M., Haque A. M., et al., “Oral Administration of Ethanolamine Glycerophospholipid Containing a High Level of Plasmalogen Improves Memory Impairment in Amyloid β‐Infused Rats,” Lipids 52 (2017): 575–585. PubMed

Wood P. L., Smith T., Lane N., Khan M. A., Ehrmantraut G., and Goodenowe D. B., “Oral Bioavailability of the Ether Lipid Plasmalogen Precursor, PPI‐1011, in the Rabbit: A New Therapeutic Strategy for Alzheimer's Disease,” Lipids in Health and Disease 10 (2011): 227. PubMed PMC

Wood P. L., Khan M. A., Smith T., et al., “In Vitro and In Vivo Plasmalogen Replacement Evaluations in Rhizomelic Chrondrodysplasia Punctata and Pelizaeus‐Merzbacher Disease Using PPI‐1011, an Ether Lipid Plasmalogen Precursor,” Lipids in Health and Disease 10 (2011): 182. PubMed PMC

Grégoire L., Smith T., Senanayake V., et al., “Plasmalogen Precursor Analog Treatment Reduces Levodopa‐Induced Dyskinesias in Parkinsonian Monkeys,” Behavioural Brain Research 286 (2015): 328–337. PubMed

Fallatah W., Smith T., Cui W., et al., “Oral Administration of a Synthetic Vinyl‐Ether Plasmalogen Normalizes Open Field Activity in a Mouse Model of Rhizomelic Chondrodysplasia Punctata,” Disease Models & Mechanisms 13 (2019): dmm.042499. PubMed PMC

Che H., Li Q., Zhang T., et al., “A Comparative Study of EPA‐Enriched Ethanolamine Plasmalogen and EPA‐Enriched Phosphatidylethanolamine on Aβ 42 Induced Cognitive Deficiency in a Rat Model of Alzheimer's Disease,” Food & Function 9 (2018): 3008‐17. PubMed

Fujino T., Yamada T., Asada T., et al., “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,” eBioMedicine 17 (2017): 199–205. PubMed PMC

Che H., Li Q., Zhang T., et al., “A Comparative Study of EPA‐Enriched Ethanolamine Plasmalogen and EPA‐Enriched Phosphatidylethanolamine on Aβ42 Induced Cognitive Deficiency in a Rat Model of Alzheimer's Disease,” Food & Function 9 (2018): 3008–3017. PubMed

Wu Y., Wang J., Deng Y., et al., “Lipid and Transcriptional Regulation in a Parkinson's Disease Mouse Model by Intranasal Vesicular and Hexosomal Plasmalogen‐Based Nanomedicines,” Advanced Healthcare Materials 13 (2024): 2304588. PubMed PMC

Schoenmaker L., Witzigmann D., Kulkarni J. A., et al., “mRNA‐Lipid Nanoparticle COVID‐19 Vaccines: Structure and Stability,” International Journal of Pharmaceutics 601 (2021): 120586. PubMed PMC

Desai N., “Challenges in Development of Nanoparticle‐Based Therapeutics,” AAPS Journal 14 (2012): 282–295. PubMed PMC

Wu Y. and Angelova A., “Recent Uses of Lipid Nanoparticles, Cell‐Penetrating and Bioactive Peptides for the Development of Brain‐Targeted Nanomedicines Against Neurodegenerative Disorders,” Nanomaterials 13 (2023): 3004. PubMed PMC

Angelova A., Angelov B., Drechsler M., Bizien T., Gorshkova Y. E., and Deng Y., “Plasmalogen‐Based Liquid Crystalline Multiphase Structures Involving Docosapentaenoyl Derivatives Inspired by Biological Cubic Membranes,” Frontiers in Cell and Development Biology 9 (2021): 617984. PubMed PMC

Wu Y., Angelov B., Deng Y., et al., “Self‐Assembled Nanocarriers of Synthetic and Natural Plasmalogens for Potential Nanomedicine Development,” Advanced Therapeutics 8 (2025): 202400093.

Angelova A., Angelov B., Garamus V. M., and Drechsler M., “A Vesicle‐To‐Sponge Transition via the Proliferation of Membrane‐Linking Pores in ω‐3 Polyunsaturated Fatty Acid‐Containing Lipid Assemblies,” Journal of Molecular Liquids 279 (2019): 518–523.

Chen C. T., Kitson A. P., Hopperton K. E., et al., “Plasma Non‐Esterified Docosahexaenoic Acid Is the Major Pool Supplying the Brain,” Scientific Reports 5 (2015): 15791. PubMed PMC

Cunnane S. C., Plourde M., Pifferi F., Bégin M., Féart C., and Barberger‐Gateau P., “Fish, Docosahexaenoic Acid and Alzheimer's Disease,” Progress in Lipid Research 48 (2009): 239–256. PubMed

Llorente A. M., Jensen C. L., Voigt R. G., Fraley J. K., Berretta M. C., and Heird W. C., “Effect of Maternal Docosahexaenoic Acid Supplementation on Postpartum Depression and Information Processing,” American Journal of Obstetrics and Gynecology 188 (2003): 1348–1353. PubMed

Kubo K., Sekine S., and Saito M., “Docosahexaenoic Acid‐Containing Phosphatidylethanolamine in the External Layer of Liposomes Protects Docosahexaenoic Acid From 2,2′‐Azobis(2‐Aminopropane)dihydrochloride‐Mediated Lipid Peroxidation,” Archives of Biochemistry and Biophysics 410 (2003): 141–148. PubMed

Eckert G. P., Chang S., Eckmann J., et al., “Liposome‐Incorporated DHA Increases Neuronal Survival by Enhancing Non‐Amyloidogenic APP Processing,” Biochimica et Biophysica Acta 1808 (2011): 236–243. PubMed

Chong S. Y., Wang X., van Bloois L., et al., “Injectable Liposomal Docosahexaenoic Acid Alleviates Atherosclerosis Progression and Enhances Plaque Stability,” Journal of Controlled Release 360 (2023): 344–364. PubMed

Deng Y., Almsherqi Z. A., Shui G., Wenk M. R., and Kohlwein S. D., “Docosapentaenoic Acid (DPA) is a Critical Determinant of Cubic Membrane Formation in Amoeba Chaos Mitochondria,” FASEB Journal 23 (2009): 2866–2871. PubMed

Calder P. C., “Polyunsaturated Fatty Acids and Inflammation,” Prostaglandins, Leukotrienes, and Essential Fatty Acids 75 (2006): 197–202. PubMed

Kumar A., Tan A., Wong J., et al., “Nanotechnology for Neuroscience: Promising Approaches for Diagnostics, Therapeutics and Brain Activity Mapping,” Advanced Functional Materials 27 (2017): 1700489. PubMed PMC

Hossain M. S., Mawatari S., and Fujino T., “Plasmalogens, the Vinyl Ether‐Linked Glycerophospholipids, Enhance Learning and Memory by Regulating Brain‐Derived Neurotrophic Factor,” Frontiers in Cell and Development Biology 10 (2022): 828282. PubMed PMC

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...