Submitted Successfully!
Thank you for your contribution! You can also upload a video entry related to this topic through the link below: https://encyclopedia.pub/user/video_add?id=35600
Check Note
2000/2000
Ver. Summary Created by Modification Content Size Created at Operation
1 -- 1794 2022-11-21 16:28:19 |
2 format Meta information modification 1794 2022-11-22 08:14:34 |
Esterification of Docosahexaenoic Acid  in Brain Diseases
Edit
Upload a video
Docosahexaenoic acid-containing lysophosphatidylcholine (DHA-LysoPC) is presented as the main transporter of DHA from blood plasma to the brain. This is related to the major facilitator superfamily domain-containing protein 2A (Mfsd2a) symporter expression in the blood–brain barrier that recognizes the various lyso-phospholipids that have choline in their polar head. In order to stabilize the DHA moiety at the sn-2 position of LysoPC, the sn-1 position was esterified by the shortest acetyl chain, creating the structural phospholipid 1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC). This small structure modification allows the maintaining of the preferential brain uptake of DHA over non-esterified DHA. Additional properties were found for AceDoPC, such as antioxidant properties, especially due to the aspirin-like acetyl moiety, as well as the capacity to generate acetylcholine in response to the phospholipase D cleavage of the polar head. Esterification of DHA within DHA-LysoPC or AceDoPC could elicit more potent neuroprotective effects against neurological diseases.
docosahexaenoic acid phospholipids lysophospholipids blood-brain-barrier
Information
View Times: 29
Entry Collection: Neurodegeneration
Revisions: 2 times (View History)
Update Time: 22 Nov 2022
Table of Contents

    1. Introduction

    Lipids are major constituents of living cells, as they are important structural components of cell membranes. Polyunsaturated fatty acids (PUFAs) are long-chain fatty acids (18 carbons or more) that contain two or more double bonds. Depending on the location of the last double bond, PUFAs are classified into families such as omega-3 (last double bond on the third carbon starting from the methyl group) and omega-6 (last double bond on the sixth carbon from the methyl group). Contrary to fatty acids that can be synthesized in the human body, some of them cannot be produced de novo and must be incorporated through diet [1]. The latter are called essential fatty acids, and they include omega-6 family precursor linoleic acid (18:2n-6) and omega-3 family precursor α-linolenic acid (LNA, 18:3n-3). By a cascade of alternating desaturase and elongase enzymatic reactions, which are common to both families, longer PUFAs are biosynthesized from their respective precursors [2]. PUFAs are mainly found esterified within glycerophospholipids present in cell membranes at the sn-1 and sn-2 positions. Glycerophospholipids are grouped by the structure of their polar head group on the sn-3 position. Their amphiphilic nature (one hydrophilic head group and two hydrophobic fatty acids) confers fluidity and selective permeability to the membranes they constitute [3][4]. They are also precursors for signaling metabolites, including eicosanoids, growth hormones, and regulators, and they participate in important physiological processes, such as anti-inflammatory or pro-inflammatory responses [5][6][7][8].
    There is a specific enrichment of essential fatty acids in human tissues, notably in the retina, brain, and heart. Contrary to arachidonic acid (ArA, 20:4n-6), which is the major PUFA of human tissues, docosahexaenoic acid (DHA, 22:6n-3) is the most prominent fatty acid in the brain, where it is considered functionally essential [9][10]. DHA concentration is especially high in neurons where it facilitates development and synaptic functions [11], with a special interest in human brain evolution [12]. A proper balance between omega-6 and omega-3 supplementation during pregnancy and infancy is required for correct neural development [13][14][15]. Along with aging, a decrease in long-chain PUFA levels in the brain has been observed, especially for DHA levels [16][17][18]. These deficiencies are correlated to a cognitive decline in normal aging but might be even more detrimental in pathological aging. In Alzheimer’s disease, decreases in PUFAs, particularly in essential fatty acids such as DHA, have been observed [19][20][21]. These results hint at a possible correlation between neurodegenerative diseases and cerebral DHA deficiency.
    DHA has many beneficial properties, especially for cerebral diseases such as Alzheimer’s disease, that were covered in numerous reviews [22][23][24][25][26]. These include pro-neurogenic, anti-oxidative, anti-inflammatory, and anti-apoptotic properties. These potent neuroprotective effects might be partly due to the conversion of DHA into active secondary metabolites such as protectins, including protectin DX [27], resolvins, and maresins [28]. DHA can also be transformed into N-Docosahexaenoylethanolamide, an endocannabinoid-like lipid mediator that has been named synaptamide due to its capacity to induce synaptogenesis, neurogenesis, and neurite outgrowth [29][30][31]. Due to its enrichment in double bonds, DHA can also provide fluidity to cell membranes [3][32][33]. As increasing its accretion into the brain through esterification into structured phospholipids improves cognitive functions in healthy brains [34], it might also heighten its neuroprotection against neuronal death.

    2. DHA-Containing Phospholipid for the Treatment of Alzheimer’s Disease

    Amyloid beta (Aβ) induced neurotoxicity can lead to the elevation of oxidative stress in the brain. In an in vitro model of Aβ1-42 neurotoxicity, primary neurons treated with PC from eggs showed less neuronal death with a reduced lactate dehydrogenase release [35]. In a rat model injected with Aβ1-40, diets enriched with DHA-containing PC (DHA-PC) or PS (DHA-PS) could increase the antioxidative enzyme superoxide dismutase (SOD) level and could reduce lipid peroxidation, inflammatory, and apoptotic levels, alongside improving spatial learning cognitive functions [36]. An increase of glutathione peroxidase (GSH-Px) and SOD activities with the improvement of cognitive deficits have also been shown in Aβ25-35-induced Alzheimer’s disease rat models treated for 30 days with DHA-PC [37]. In humans, a prospective follow-up study showed that subjects with baseline plasma DHA-PC levels in the upper quartile had 39% and 47% lower risks of developing Alzheimer disease and all-cause dementia, respectively, compared with participants with levels in the lower 3 quartiles [38].
    In a study of senescence-accelerated prone 8 (SAMP8), mice were fed with a high-fat diet, as a model of Alzheimer’s disease, or with a diet enriched with DHA-PC or DHA-PS, which both increased the activity of antioxidative enzymes GSH-Px and SOD while decreasing malondialdehyde, a marker of lipid peroxidation [39]. The mice also showed enhanced cognitive performances, improved neuroprotection through decreased neuroinflammation and apoptosis, and amelioration in Aβ pathology.
    The observed improvement of brain health and cognitive functions in the pathology of Alzheimer’s disease could be due not only to the neuroprotective effects of DHA (anti-inflammatory, anti-oxidative, and anti-apoptotic) but also to the beneficial transport of DHA through the BBB, increasing its bioavailability in neural cells. Another working hypothesis is that DHA can also prevent the accumulation of Aβ peptides [22][40][41][42] and the formation of fibrils [43][44][45], thus decreasing the apoptotic effects of oligomers. DHA is suggested to act on multiple pleiotropic mechanisms, leading to beneficial effects on the pathology of Alzheimer’s disease [21][23]. An additional hypothesis is that the choline moiety in the polar head of PC is crucial for neuroprotection, as Ko M. et al. reported that PC but not PS was able to protect against Aβ-induced cell toxicity [35].

    3. Potential Therapy to Other Neurological Diseases

    Mice treated with 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) to mimic oxidative damage induced by the pathology of Parkinson’s disease were fed with DHA- and eicosapentaenoic acid (EPA)-containing phospholipids, which were extracted from squid roe and contained mainly DHA-PC, DHA-containing PE (DHA-PE), and DHA-LysoPC [46]. Compared to the control group (only treated with MPTP), mice fed with DHA/EPA-PC had increased levels of antioxidative enzymes (GSH-Px and SOD) along with a reduction of motor impairments and a decrease of pro-apoptotic markers. Further study on the same model showed that a DHA-PC enriched diet could elevate activities of glutathione and SOD, alleviate the loss of dopaminergic neurons following MPTP treatment (notably through the reduction of pro-apoptotic markers), and dampen cognitive impairments in locomotor activity [47]. Parkinson’s disease is mainly characterized by the abnormal aggregation of α-synuclein protein forming Lewy bodies, an imbalance in the levels of reactive oxygen species, and the loss of dopaminergic neurons. Omega-3 fatty acids, and particularly DHA, can interact with α-synuclein to prevent its detrimental oligomerization [48][49][50]. Another pathway of action of DHA is the modulation of dopamine-induced neurodegeneration [51][52] and the enhancement of anti-oxidative pathways [52].
    In a model of dementia induced by short-term memory and learning impairment by treatment with scopolamine, mice fed with squid PC (enriched in DHA) performed better in a spatial-learning memory test and had increased antioxidative activity and a lower lipid peroxidation level compared to the control group [53]. Interestingly, elevated levels of acetylcholinesterase activity induced by scopolamine injection were reduced with squid PC treatment. In a following study by the same research group, it was shown that a DHA-deficient diet could lead to further damage due to scopolamine treatment through oxidative stress, apoptosis, inflammation, and delayed neurodevelopment [54], hinting at possible preventive therapy through a balanced omega-3 diet.
    The potential use of DHA’s beneficial properties on neuropsychiatric disorders is also currently under study [55]. Through its potency to reduce anti-inflammation and to promote neurogenesis, DHA was shown to reduce inflammatory markers in both in vitro and clinical studies [56]. The authors found correlations between higher levels of anti-inflammatory markers linked to DHA and lower levels of depressive symptoms. Similarly, in an in vivo study of forced swimming tests on rats, a decrease of inflammatory cytokines and an increase in serotonin levels were observed with omega-3 supplementation, suggesting anti-depressant effects of DHA [57]. Interestingly, dietary supplementation of DHA-containing phospholipids in a mice model of depression rescued depression-like behavior and inhibited neuroinflammation, suggesting increased effects on depression through DHA esterification in phospholipids [58].

    4. AceDoPC as a Potential Antioxidant and Neurogenesis Inducer

    In the case of AceDoPC initially, sn2-DHA-LysoPC was acetylated at the sn-1 position to prevent the migration of DHA from the sn-2 position as discussed above [59], but it appears that such an acetylation also confers some antioxidant activities to AceDoPC compared to non-esterified DHA. This was observed in an experimental stroke with a more significant lower size of post-stroke lesions and decreased oxidative stress after AceDoPC intravenous injection [60]. In an in vitro model of stroke on adult neural stem cells, strong antioxidant actions of AceDoPC could be seen on prostanoids and lipoxygenase product formation, with lipoxygenase products from ArA (leukotriene B4, LTB4, and 15-Hydroxyeicosatetraenoic acid, 15-HETE) being surprisingly more affected than prostanoids [61].
    The inhibition of prostanoid formation could be explained by the inhibition of cyclooxygenases (COX), as shown in using purified COX-1 and COX-2 [62], suggesting an aspirin-like effect of the acetyl-containing AceDoPC. Beyond these effects on lipid metabolism, the treatment of AceDoPC by phospholipase D (PLD) leads to acetylcholine formation, likely by the combination of the acetyl group of the molecule with the released choline moiety due to PLD cleavage process [62]. AceDoPC also acts as an inhibitor of lipopolysaccharide-induced neuroinflammation, both in vitro and in vivo, with some specificities compared to DHA-PC [63].
    In adult neural stem cells, nanomolar concentrations of AceDoPC increased neurogenesis by 2.5 fold (compared to the control) in the presence of AceDoPC, while 1.5 fold increase with non-esterified DHA was observed [61]. Enhanced neurogenesis by AceDoPC was even higher under pathological conditions (under hypoxia/ischemia-like conditions) while no effect was observed on gliogenesis. Another phospholipid that is structurally similar to AceDoPC but contains protectin DX, a metabolite of DHA, at the sn-2 position, was also produced [64]. This phospholipid, labeled AceDxPC, might enhance the beneficial effects of AceDoPC.
    An additional interest of AceDoPC is due to the quick loss of its acetyl moiety [65] then releasing sn-2-DHA- LysoPC (with DHA at the sn-2 position), which is quickly isomerized into sn-1-DHA-LysoPC (with DHA at the sn-1 position) [66], a substrate for producing synaptamide [67].

    References

    1. Spector, A.A.; Kim, H.-Y. Discovery of essential fatty acids. J. Lipid Res. 2015, 56, 11–21.
    2. Leonard, A.; Pereira, S.L.; Sprecher, H.; Huang, Y.-S. Elongation of long-chain fatty acids. Prog. Lipid Res. 2004, 43, 36–54.
    3. Stillwell, W.; Wassall, S.R. Docosahexaenoic acid: Membrane properties of a unique fatty acid. Chem. Phys. Lipids 2003, 126, 1–27.
    4. Yang, X.; Sheng, W.; Sun, G.Y.; Lee, J.C.-M. Effects of fatty acid unsaturation numbers on membrane fluidity and α-secretase-dependent amyloid precursor protein processing. Neurochem. Int. 2011, 58, 321–329.
    5. Lagarde, M.; Bernoud-Hubac, N.; Calzada, C.; Véricel, E.; Guichardant, M. Lipidomics of essential fatty acids and oxygenated metabolites. Mol. Nutr. Food Res. 2013, 57, 1347–1358.
    6. Kuda, O. Bioactive metabolites of docosahexaenoic acid. Biochimie 2017, 136, 12–20.
    7. Christie, W.W.; Harwood, J.L. Oxidation of polyunsaturated fatty acids to produce lipid mediators. Essays Biochem. 2020, 64, 401–421.
    8. Das, U.N. Essential Fatty Acids and Their Metabolites in the Pathobiology of Inflammation and Its Resolution. Biomolecules 2021, 11, 1873.
    9. Crawford, M.; Doyle, W.; Leaf, A.; Leighfield, M.; Ghebremeskel, K.; Phylactos, A. Nutrition and Neurodevelopmental Disorders. Nutr. Health 1993, 9, 81–97.
    10. Salem, N.; Litman, B.; Kim, H.-Y.; Gawrisch, K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 2001, 36, 945–959.
    11. Cao, D.; Kevala, K.; Kim, J.; Moon, H.-S.; Jun, S.B.; Lovinger, D.; Kim, H.-Y. Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J. Neurochem. 2009, 111, 510–521.
    12. Crawford, M.A.; Bloom, M.; Broadhurst, C.L.; Schmidt, W.F.; Cunnane, S.C.; Galli, C.; Gehbremeskel, K.; Linseisen, F.; Lloyd-Smith, J.; Parkington, J. Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain. Lipids 1999, 34, S39–S47.
    13. Ryan, A.S.; Astwood, J.D.; Gautier, S.; Kuratko, C.N.; Nelson, E.B.; Salem, N. Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: A review of human studies. Prostaglandins Leukot. Essent. Fat. Acids 2010, 82, 305–314.
    14. Guesnet, P.; Alessandri, J.-M. Docosahexaenoic acid (DHA) and the developing central nervous system (CNS)–Implications for dietary recommendations. Biochimie 2011, 93, 7–12.
    15. Sakayori, N.; Kikkawa, T.; Tokuda, H.; Kiryu, E.; Yoshizaki, K.; Kawashima, H.; Yamada, T.; Arai, H.; Kang, J.X.; Katagiri, H.; et al. Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites. Stem Cells 2016, 34, 470–482.
    16. López, G.; de Boschero, M.I.; Castagnet, P.; Giusto, N. Age-associated changes in the content and fatty acid composition of brain glycerophospholipids. Comp. Biochem. Physiol. Part B Biochem. Mol. Biol. 1995, 112, 331–343.
    17. Giusto, N.M.; Salvador, G.A.; Castagnet, P.I.; Pasquaré, S.J.; De Boschero, M.G.I. Age-associated changes in central nervous system glycerolipid composition and metabolism. Neurochem. Res. 2002, 27, 1513–1523.
    18. Bourre, J.M. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J. Nutr. Health Aging 2004, 8, 163–174. Available online: http://www.ncbi.nlm.nih.gov/pubmed/15129302 (accessed on 21 November 2016).
    19. Conquer, J.A.; Tierney, M.C.; Zecevic, J.; Bettger, W.J.; Fisher, R.H. Fatty acid analysis of blood plasma of patients with alzheimer’s disease, other types of dementia, and cognitive impairment. Lipids 2000, 35, 1305–1312.
    20. Fabelo, N.; Martín, V.; Marín, R.; Moreno, D.; Ferrer, I.; Díaz, M. Altered lipid composition in cortical lipid rafts occurs at early stages of sporadic Alzheimer’s disease and facilitates APP/BACE1 interactions. Neurobiol. Aging 2014, 35, 1801–1812.
    21. Mesa-Herrera, F.; Taoro-González, L.; Valdés-Baizabal, C.; Diaz, M.; Marín, R. Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers. Int. J. Mol. Sci. 2019, 20, 3810.
    22. Grimm, M.O.; Kuchenbecker, J.; Grösgen, S.; Burg, V.K.; Hundsdörfer, B.; Rothhaar, T.L.; Friess, P.; de Wilde, M.C.; Broersen, L.M.; Penke, B.; et al. Docosahexaenoic Acid Reduces Amyloid β Production via Multiple Pleiotropic Mechanisms. J. Biol. Chem. 2011, 286, 14028–14039.
    23. Belkouch, M.; Hachem, M.; Elgot, A.; Lo Van, A.; Picq, M.; Guichardant, M.; Lagarde, M.; Bernoud-Hubac, N. The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer’s disease. J. Nutr. Biochem. 2016, 38, 1–11.
    24. Lo Van, A.; Sakayori, N.; Hachem, M.; Belkouch, M.; Picq, M.; Lagarde, M.; Osumi, N.; Bernoud-Hubac, N. Mechanisms of DHA transport to the brain and potential therapy to neurodegenerative diseases. Biochimie 2016, 130, 163–167.
    25. Hachem, M.; Nacir, H. Emerging Role of Phospholipids and Lysophospholipids for Improving Brain Docosahexaenoic Acid as Potential Preventive and Therapeutic Strategies for Neurological Diseases. Int. J. Mol. Sci. 2022, 23, 3969.
    26. Mora, I.; Arola, L.; Caimari, A.; Escoté, X.; Puiggròs, F. Structured Long-Chain Omega-3 Fatty Acids for Improvement of Cognitive Function during Aging. Int. J. Mol. Sci. 2022, 23, 3472.
    27. Liu, M.; Boussetta, T.; Makni-Maalej, K.; Fay, M.; Driss, F.; El-Benna, J.; Lagarde, M.; Guichardant, M. Protectin DX, a Double Lipoxygenase Product of DHA, Inhibits Both ROS Production in Human Neutrophils and Cyclooxygenase Activities. Lipids 2014, 49, 49–57.
    28. Serhan, C.N. Novel Chemical Mediators in the Resolution of Inflammation: Resolvins and Protectins. Anesthesiol. Clin. N. Am. 2006, 24, 341–364.
    29. Kim, H.Y.; Moon, H.S.; Cao, D.; Lee, J.; Kevala, K.; Jun, S.B.; Lovinger, M.D.; Akbar, M.; Huang, B.X. N-Docosahexaenoylethanolamide promotes development of hippocampal neurons. Biochem. J. 2011, 435, 327–336.
    30. Kim, H.-Y.; Spector, A.A. Synaptamide, endocannabinoid-like derivative of docosahexaenoic acid with cannabinoid-independent function. Prostaglandins Leukot. Essent. Fat. Acids 2013, 88, 121–125.
    31. Tyrtyshnaia, A.; Bondar, A.; Konovalova, S.; Manzhulo, I. Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain. Int. J. Mol. Sci. 2021, 22, 12779.
    32. Hashimoto, M.; Hossain, S.; Shimada, T.; Shido, O. Docosahexaenoic acid-induced protective effect against impaired learning in amyloid β-Infused rats is associated with increased synaptosomal membrane fluidity. Clin. Exp. Pharmacol. Physiol. 2006, 33, 934–939.
    33. Hashimoto, M.; Hossain, S.; Al Mamun, A.; Matsuzaki, K.; Arai, H. Docosahexaenoic acid: One molecule diverse functions. Crit. Rev. Biotechnol. 2016, 37, 579–597.
    34. Sugasini, D.; Thomas, R.; Yalagala, P.C.R.; Tai, L.M.; Subbaiah, P.V. Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice. Sci. Rep. 2017, 7, 11263.
    35. Ko, M.; Hattori, T.; Abdullah, M.; Gong, J.-S.; Yamane, T.; Michikawa, M. Phosphatidylcholine protects neurons from toxic effects of amyloid β-protein in culture. Brain Res. 2016, 1642, 376–383.
    36. Wen, M.; Ding, L.; Zhang, L.; Zhou, M.; Xu, J.; Wang, J.; Wang, Y.; Xue, C. DHA-PC and DHA-PS improved Aβ1–40 induced cognitive deficiency uncoupled with an increase in brain DHA in rats. J. Funct. Foods 2016, 22, 417–430.
    37. Qu, M.-H.; Yang, X.; Wang, Y.; Tang, Q.; Han, H.; Wang, J.; Du Wang, G.; Xue, C.; Gao, Z. Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aβ23-35-Induced Alzheimer’s Disease Rat Model. Curr. Top. Med. Chem. 2015, 16, 558–564.
    38. Schaefer, E.J.; Bongard, V.; Beiser, A.; Lamon-Fava, S.; Robins, S.J.; Au, R.; Tucker, K.; Kyle, D.J.; Wilson, P.W.F.; Wolf, P.A. Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease. Arch. Neurol. 2006, 63, 1545–1550.
    39. Zhou, M.-M.; Ding, L.; Wen, M.; Che, H.-X.; Huang, J.-Q.; Zhang, T.-T.; Xue, C.-H.; Mao, X.-Z.; Wang, Y.-M. Mechanisms of DHA-enriched phospholipids in improving cognitive deficits in aged SAMP8 mice with high-fat diet. J. Nutr. Biochem. 2018, 59, 64–75.
    40. Green, K.N.; Martínez-Coria, H.; Khashwji, H.; Hall, E.B.; Yurko-Mauro, K.A.; Ellis, L.; LaFerla, F.M. Dietary Docosahexaenoic Acid and Docosapentaenoic Acid Ameliorate Amyloid- and Tau Pathology via a Mechanism Involving Presenilin 1 Levels. J. Neurosci. 2007, 27, 4385–4395.
    41. Lim, G.P.; Calon, F.; Morihara, T.; Yang, F.; Teter, B.; Ubeda, O.; Salem, N.; Frautschy, S.A.; Cole, G.M. A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model. J. Neurosci. 2005, 25, 3032–3040.
    42. Teng, E.; Taylor, K.; Bilousova, T.; Weiland, D.; Pham, T.; Zuo, X.; Yang, F.; Chen, P.-P.; Glabe, C.G.; Takacs, A.; et al. Dietary DHA supplementation in an APP/PS1 transgenic rat model of AD reduces behavioral and Aβ pathology and modulates Aβ oligomerization. Neurobiol. Dis. 2015, 82, 552–560.
    43. Hashimoto, M.; Shahdat, H.M.; Yamashita, S.; Katakura, M.; Tanabe, Y.; Fujiwara, H.; Gamoh, S.; Miyazawa, T.; Arai, H.; Shimada, T.; et al. Docosahexaenoic acid disrupts in vitro amyloid β1–40 fibrillation and concomitantly inhibits amyloid levels in cerebral cortex of Alzheimer’s disease model rats. J. Neurochem. 2008, 107, 1634–1646.
    44. Hashimoto, M.; Shahdat, H.M.; Katakura, M.; Tanabe, Y.; Gamoh, S.; Miwa, K.; Shimada, T.; Shido, O. Effects of docosahexaenoic acid on in vitro amyloid beta peptide 25–35 fibrillation. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 2009, 1791, 289–296.
    45. Eto, M.; Hashimoto, T.; Shimizu, T.; Iwatsubo, T. Characterization of the unique In Vitro effects of unsaturated fatty acids on the formation of amyloid β fibrils. PLoS ONE 2019, 14, e0219465.
    46. Wang, D.; Zhang, L.; Wen, M.; Du, L.; Gao, X.; Xue, C.; Xu, J.; Wang, Y. Enhanced neuroprotective effect of DHA and EPA-enriched phospholipids against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced oxidative stress in mice brain. J. Funct. Foods 2016, 25, 385–396.
    47. Wang, C.; Wang, D.; Xu, J.; Yanagita, T.; Xue, C.; Zhang, T.; Wang, Y. DHA enriched phospholipids with different polar groups (PC and PS) had different improvements on MPTP-induced mice with Parkinson’s disease. J. Funct. Foods 2018, 45, 417–426.
    48. Sharon, R.; Bar-Joseph, I.; Frosch, M.P.; Walsh, D.M.; Hamilton, J.A.; Selkoe, D.J. The Formation of Highly Soluble Oligomers of α-Synuclein Is Regulated by Fatty Acids and Enhanced in Parkinson’s Disease. Neuron 2003, 37, 583–595.
    49. Broersen, K.; van den Brink, D.; Fraser, G.; Goedert, M.; Davletov, B. α-Synuclein Adopts an α-Helical Conformation in the Presence of Polyunsaturated Fatty Acids To Hinder Micelle Formation. Biochemistry 2006, 45, 15610–15616.
    50. Fecchio, C.; Palazzi, L.; de Laureto, P.P. α-Synuclein and Polyunsaturated Fatty Acids: Molecular Basis of the Interaction and Implication in Neurodegeneration. Molecules 2018, 23, 1531.
    51. Chitre, N.M.; Wood, B.J.; Ray, A.; Moniri, N.H.; Murnane, K.S. Docosahexaenoic acid protects motor function and increases dopamine synthesis in a rat model of Parkinson’s disease via mechanisms associated with increased protein kinase activity in the striatum. Neuropharmacology 2020, 167, 107976.
    52. Lamontagne-Proulx, J.; Coulombe, K.; Dahhani, F.; Côté, M.; Guyaz, C.; Tremblay, C.; Di Marzo, V.; Flamand, N.; Calon, F.; Soulet, D. Effect of Docosahexaenoic Acid (DHA) at the Enteric Level in a Synucleinopathy Mouse Model. Nutrients 2021, 13, 4218.
    53. Zhou, M.-M.; Xue, Y.; Sun, S.-H.; Wen, M.; Li, Z.-J.; Xu, J.; Wang, J.-F.; Yanagita, T.; Wang, Y.-M.; Xue, C.-H. Effects of different fatty acids composition of phosphatidylcholine on brain function of dementia mice induced by scopolamine. Lipids Health Dis. 2016, 15, 135.
    54. Wang, D.-D.; Wu, F.; Ding, L.; Shi, H.-H.; Xue, C.-H.; Wang, Y.-M.; Zhang, T.-T. Dietary n–3 PUFA Deficiency Increases Vulnerability to Scopolamine-Induced Cognitive Impairment in Male C57BL/6 Mice. J. Nutr. 2021, 151, 2206–2214.
    55. Hashimoto, M.; Maekawa, M.; Katakura, M.; Hamazaki, K.; Matsuoka, Y. Possibility of Polyunsaturated Fatty Acids for the Prevention and Treatment of Neuropsychiatric Illnesses. J. Pharmacol. Sci. 2014, 124, 294–300.
    56. Borsini, A.; Nicolaou, A.; Camacho-Muñoz, D.; Kendall, A.C.; Di Benedetto, M.G.; Giacobbe, J.; Su, K.-P.; Pariante, C.M. Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: Relevance for major depression and for human hippocampal neurogenesis. Mol. Psychiatry 2021, 26, 6773–6788.
    57. Park, Y.; Moon, H.-J.; Kim, S.-H. N-3 polyunsaturated fatty acid consumption produces neurobiological effects associated with prevention of depression in rats after the forced swimming test. J. Nutr. Biochem. 2012, 23, 924–928.
    58. Wang, C.; Wang, J.; Shi, H.; Zhao, Y.; Yang, J.; Wang, Y.; Yanagita, T.; Xue, C.; Zhang, T. DHA-Enriched Phospholipids Exhibit Anti-Depressant Effects by Immune and Neuroendocrine Regulation in Mice: A Study on Dose- and Structure-Activity Relationship. Mol. Nutr. Food Res. 2022, 2200089.
    59. Polette, A.; Deshayes, C.; Chantegrel, B.; Croset, M.; Armstrong, J.M.; Lagarde, M. Synthesis of acetyl, docosahexaenoyl-glycerophosphocholine and its characterization using nuclear magnetic resonance. Lipids 1999, 34, 1333–1337.
    60. Chauveau, F.; Cho, T.-H.; Perez, M.; Guichardant, M.; Riou, A.; Aguettaz, P.; Picq, M.; Lagarde, M.; Berthezene, Y.; Nighoghossian, N.; et al. Brain-Targeting Form of Docosahexaenoic Acid for Experimental Stroke Treatment: MRI Evaluation and Anti-Oxidant Impact. Curr. Neurovascular Res. 2011, 8, 95–102.
    61. Lo Van, A.; Sakayori, N.; Hachem, M.; Belkouch, M.; Picq, M.; Fourmaux, B.; Lagarde, M.; Osumi, N.; Bernoud-Hubac, N. Targeting the Brain with a Neuroprotective Omega-3 Fatty Acid to Enhance Neurogenesis in Hypoxic Condition in Culture. Mol. Neurobiol. 2018, 56, 986–999.
    62. Lagarde, M.; Vericel, E.; Picq, M.; Guichardant, M.; Bernoud-Hubac, N.; Fourmaux, B. AceFaPC for the Treatment of Acetylcholine-Dependent Diseases. WO Patent WO-2018162617-A1, 8 March 2018.
    63. Fourrier, C.; Remus-Borel, J.; Greenhalgh, A.D.; Guichardant, M.; Bernoud-Hubac, N.; Lagarde, M.; Joffre, C.; Layé, S. Docosahexaenoic acid-containing choline phospholipid modulates LPS-induced neuroinflammation in vivo and in microglia in vitro. J. Neuroinflamm. 2017, 14, 170.
    64. Lo Van, A.; Fourmaux, B.; Picq, M.; Guichardant, M.; Lagarde, M.; Bernoud-Hubac, N. Synthesis and Identification of AceDoxyPC, a Protectin-Containing Structured Phospholipid, Using Liquid Chromatography/Mass Spectrometry. Lipids 2017, 52, 751–761.
    65. Hachem, M.; Géloën, A.; Lo Van, A.; Foumaux, B.; Fenart, L.; Gosselet, F.; Da Silva, P.; Breton, G.; Lagarde, M.; Picq, M.; et al. Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid. Mol. Neurobiol. 2016, 53, 3205–3215.
    66. Croset, M.; Brossard, N.; Polette, A.; Lagarde, M. Characterization of plasma unsaturated lysophosphatidylcholines in human and rat. Biochem. J. 2000, 345, 61–67.
    67. Kevala, K.; Lagarde, M.; Spector, A.; Kim, H.-Y. Biosynthesis of N-Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells. Int. J. Mol. Sci. 2020, 21, 8768.
    More
    Information
    Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , ,
    View Times: 29
    Entry Collection: Neurodegeneration
    Revisions: 2 times (View History)
    Update Time: 22 Nov 2022
    Table of Contents
      1000/1000

      Confirm

      Are you sure to Delete?

      Video Upload Options

      Do you have a full video?
      Cite
      If you have any further questions, please contact Encyclopedia Editorial Office.
      Van, A.L.; Bernoud-Hubac, N.; Lagarde, M. Esterification of Docosahexaenoic Acid  in Brain Diseases. Encyclopedia. Available online: https://encyclopedia.pub/entry/35600 (accessed on 01 December 2022).
      Van AL, Bernoud-Hubac N, Lagarde M. Esterification of Docosahexaenoic Acid  in Brain Diseases. Encyclopedia. Available at: https://encyclopedia.pub/entry/35600. Accessed December 01, 2022.
      Van, Amanda Lo, Nathalie Bernoud-Hubac, Michel Lagarde. "Esterification of Docosahexaenoic Acid  in Brain Diseases," Encyclopedia, https://encyclopedia.pub/entry/35600 (accessed December 01, 2022).
      Van, A.L., Bernoud-Hubac, N., & Lagarde, M. (2022, November 21). Esterification of Docosahexaenoic Acid  in Brain Diseases. In Encyclopedia. https://encyclopedia.pub/entry/35600
      Van, Amanda Lo, et al. ''Esterification of Docosahexaenoic Acid  in Brain Diseases.'' Encyclopedia. Web. 21 November, 2022.
      Top
      Feedback