Postmortem Fatty Acid Abnormalities in the Cerebellum of Patients with Essential Tremor.
Essential tremor (ET)
Fatty acids
Glycerophospholipids
Omega-3 polyunsaturated fatty acids (ω-3 PUFA)
Journal
Cerebellum (London, England)
ISSN: 1473-4230
Titre abrégé: Cerebellum
Pays: United States
ID NLM: 101089443
Informations de publication
Date de publication:
31 Aug 2024
31 Aug 2024
Historique:
accepted:
21
08
2024
medline:
1
9
2024
pubmed:
1
9
2024
entrez:
31
8
2024
Statut:
aheadofprint
Résumé
Fatty acids play many critical roles in brain function but have not been investigated in essential tremor (ET), a frequent movement disorder suspected to involve cerebellar dysfunction. Here, we report a postmortem comparative analysis of fatty acid profiles by gas chromatography in the cerebellar cortex from ET patients (n = 15), Parkinson's disease (PD) patients (n = 15) and Controls (n = 17). Phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI)/ phosphatidylserine (PS) were separated by thin-layer chromatography and analyzed separately. First, the total amounts of fatty acids retrieved from the cerebellar cortex were lower in ET patients compared with PD patients, including monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA). The diagnosis of ET was associated with lower cerebellar levels of saturated fatty acids (SFA) and PUFA (DHA and ARA) in the PE fraction specifically, but with a higher relative content of dihomo-γ-linolenic acid (DGLA; 20:3 ω-6) in the PC fraction. In contrast, a diagnosis of PD was associated with higher absolute concentrations of SFA, MUFA and ω-6 PUFA in the PI + PS fractions. However, relative PI + PS contents of ω-6 PUFA were lower in both PD and ET patients. Finally, linear regression analyses showed that the ω-3:ω-6 PUFA ratio was positively associated with age of death, but inversely associated with insoluble α-synuclein. Although it remains unclear how these FA changes in the cerebellum are implicated in ET or PD pathophysiology, they may be related to an ongoing neurodegenerative process or to dietary intake differences. The present findings provide a window of opportunity for lipid-based therapeutic nutritional intervention.
Identifiants
pubmed: 39215908
doi: 10.1007/s12311-024-01736-4
pii: 10.1007/s12311-024-01736-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fonds de Recherche du Québec - Santé
ID : 253895
Informations de copyright
© 2024. The Author(s).
Références
Louis ED, Ottman R. How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data. Tremor Other Hyperkinet Mov (N Y). 2014;4:259.
doi: 10.5334/tohm.198
Louis ED, McCreary M. How common is essential Tremor? Update on the Worldwide Prevalence of essential tremor. Tremor Other Hyperkinet Mov (N Y). 2021;11:28.
doi: 10.5334/tohm.632
Thenganatt MA, Louis ED. Distinguishing essential tremor from Parkinson’s disease: bedside tests and laboratory evaluations. Expert Rev Neurother. 2012;12(6):687–96.
pubmed: 22650171
pmcid: 3475963
doi: 10.1586/ern.12.49
Louis ED, Faust PL. Essential tremor pathology: neurodegeneration and reorganization of neuronal connections. Nat Rev Neurol. 2020.
Louis ED, Faust PL, Vonsattel JPG, Honig LS, Rajput A, Robinson CA, et al. Neuropathological changes in essential tremor: 33 cases compared with 21 controls. Brain. 2007;130(12):3297–307.
pubmed: 18025031
doi: 10.1093/brain/awm266
Louis ED, Martuscello RT, Gionco JT, Hartstone WG, Musacchio JB, Portenti M, et al. Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains. Acta Neuropathol. 2023;145(3):265–83.
pubmed: 36607423
pmcid: 10461794
doi: 10.1007/s00401-022-02535-z
Welton T, Cardoso F, Carr JA, Chan LL, Deuschl G, Jankovic J, et al. Essential tremor. Nat Rev Dis Primers. 2021;7(1):83.
pubmed: 34764294
doi: 10.1038/s41572-021-00314-w
Bruce KD, Zsombok A, Eckel RH. Lipid Processing in the brain: a Key Regulator of systemic metabolism. Front Endocrinol (Lausanne). 2017;8:60.
pubmed: 28421037
doi: 10.3389/fendo.2017.00060
Calon F. Modulation des lipides du cerveau par l’alimentation: études chez des modèles animaux de maladies neurodégénératives. Cahiers De Nutr et de Diététique. 2014;49(3):120–5.
doi: 10.1016/j.cnd.2014.03.003
Söderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem. 1990;54(2):415–23.
pubmed: 2299344
doi: 10.1111/j.1471-4159.1990.tb01889.x
Ouellet M, Emond V, Chen CT, Julien C, Bourasset F, Oddo S, et al. Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebral perfusion study. Neurochem Int. 2009;55(7):476–82.
pubmed: 19442696
doi: 10.1016/j.neuint.2009.04.018
Hamilton LK, Dufresne M, Joppé SE, Petryszyn S, Aumont A, Calon F, et al. Aberrant lipid metabolism in the Forebrain Niche suppresses adult neural stem cell proliferation in an animal model of Alzheimer’s Disease. Cell Stem Cell. 2015;17(4):397–411.
pubmed: 26321199
doi: 10.1016/j.stem.2015.08.001
Calon F. Omega-3 polyunsaturated fatty acids in Alzheimer’s disease: key questions and partial answers. Curr Alzheimer Res. 2011;8(5):470–8.
pubmed: 21605051
doi: 10.2174/156720511796391881
Arsenault D, Julien C, Chen CT, Bazinet RP, Calon F. Dietary intake of unsaturated fatty acids modulates physiological properties of entorhinal cortex neurons in mice. J Neurochem. 2012;122(2):427–43.
pubmed: 22551210
doi: 10.1111/j.1471-4159.2012.07772.x
Phivilay A, Julien C, Tremblay C, Berthiaume L, Julien P, Giguère Y, et al. High dietary consumption of trans fatty acids decreases brain docosahexaenoic acid but does not alter amyloid-beta and tau pathologies in the 3xTg-AD model of Alzheimer’s disease. Neuroscience. 2009;159(1):296–307.
pubmed: 19135506
doi: 10.1016/j.neuroscience.2008.12.006
Kaplan RJ, Greenwood CE. Dietary saturated fatty acids and brain function. Neurochem Res. 1998;23(5):615–26.
pubmed: 9566599
doi: 10.1023/A:1022478503367
Bazinet RP, Laye S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci. 2014;15(12):771–85.
pubmed: 25387473
doi: 10.1038/nrn3820
Salem N, Vandal M, Calon F. The benefit of docosahexaenoic acid for the adult brain in aging and dementia. Prostaglandins Leukot Essent Fat Acids. 2015;92:15–22.
doi: 10.1016/j.plefa.2014.10.003
Joffre C, Nadjar A, Lebbadi M, Calon F, Laye S. n-3 LCPUFA improves cognition: the young, the old and the sick. Prostaglandins Leukot Essent Fat Acids. 2014;91(1–2):1–20.
doi: 10.1016/j.plefa.2014.05.001
Julien C, Berthiaume L, Hadj-Tahar A, Rajput AH, Bedard PJ, Di Paolo T, et al. Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys. Neurochem Int. 2006;48(5):404–14.
pubmed: 16442670
doi: 10.1016/j.neuint.2005.12.002
Bousquet M, Calon F, Cicchetti F. Impact of ω-3 fatty acids in Parkinson’s disease. Ageing Res Rev. 2011;10(4):453–63.
pubmed: 21414422
doi: 10.1016/j.arr.2011.03.001
Hernando S, Requejo C, Herran E, Ruiz-Ortega JA, Morera-Herreras T, Lafuente JV, et al. Beneficial effects of n-3 polyunsaturated fatty acids administration in a partial lesion model of Parkinson’s disease: the role of glia and NRf2 regulation. Neurobiol Dis. 2019;121:252–62.
pubmed: 30296616
doi: 10.1016/j.nbd.2018.10.001
Bazan NG, Colangelo V, Lukiw WJ. Prostaglandins and other lipid mediators in Alzheimer’s disease. Prostaglandins Other Lipid Mediat. 2002;68–69:197–210.
pubmed: 12432919
doi: 10.1016/S0090-6980(02)00031-X
Teismann P, Tieu K, Choi DK, Wu DC, Naini A, Hunot S, et al. Cyclooxygenase-2 is instrumental in Parkinson’s disease neurodegeneration. Proc Natl Acad Sci USA. 2003;100(9):5473–8.
pubmed: 12702778
pmcid: 154369
doi: 10.1073/pnas.0837397100
Kerdiles O, Layé S, Calon F. Omega-3 polyunsaturated fatty acids and brain health: preclinical evidence for the prevention of neurodegenerative diseases. Trends Food Sci Technol. 2017;69:203–13.
doi: 10.1016/j.tifs.2017.09.003
Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, et al. Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron. 2004;43(5):633–45.
pubmed: 15339646
pmcid: 2442162
doi: 10.1016/j.neuron.2004.08.013
Arsenault D, Julien C, Tremblay C, Calon F. DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS ONE. 2011;6(2):e17397.
pubmed: 21383850
pmcid: 3044176
doi: 10.1371/journal.pone.0017397
Calon F, Lim GP, Morihara T, Yang F, Ubeda O, Salem N, et al. Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer’s disease. Eur J Neurosci. 2005;22(3):617–26.
pubmed: 16101743
doi: 10.1111/j.1460-9568.2005.04253.x
Casali BT, Corona AW, Mariani MM, Karlo JC, Ghosal K, Landreth GE. Omega-3 fatty acids augment the actions of Nuclear receptor agonists in a mouse model of Alzheimer’s Disease. J Neurosci. 2015;35(24):9173–81.
pubmed: 26085639
pmcid: 4469742
doi: 10.1523/JNEUROSCI.1000-15.2015
Hooijmans CR, Van der Zee CE, Dederen PJ, Brouwer KM, Reijmer YD, van Groen T, et al. DHA and cholesterol containing diets influence Alzheimer-like pathology, cognition and cerebral vasculature in APPswe/PS1dE9 mice. Neurobiol Dis. 2009;33(3):482–98.
pubmed: 19130883
doi: 10.1016/j.nbd.2008.12.002
Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, et al. A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci. 2005;25(12):3032–40.
pubmed: 15788759
pmcid: 6725084
doi: 10.1523/JNEUROSCI.4225-04.2005
Perez SE, Berg BM, Moore KA, He B, Counts SE, Fritz JJ, et al. DHA diet reduces AD pathology in young APPswe/PS1 Delta E9 transgenic mice: possible gender effects. J Neurosci Res. 2010;88(5):1026–40.
pubmed: 19859965
pmcid: 3118087
doi: 10.1002/jnr.22266
Cunnane SC, Plourde M, Pifferi F, Bégin M, Féart C, Barberger-Gateau P. Fish, docosahexaenoic acid and Alzheimer’s disease. Prog Lipid Res. 2009;48(5):239–56.
pubmed: 19362576
doi: 10.1016/j.plipres.2009.04.001
Fraser T, Tayler H, Love S. Fatty acid composition of frontal, temporal and parietal neocortex in the normal human brain and in Alzheimer’s disease. Neurochem Res. 2010;35(3):503–13.
pubmed: 19904605
doi: 10.1007/s11064-009-0087-5
Cunnane SC, Schneider JA, Tangney C, Tremblay-Mercier J, Fortier M, Bennett DA, et al. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer’s disease. J Alzheimers Dis. 2012;29(3):691–7.
pubmed: 22466064
pmcid: 3409580
doi: 10.3233/JAD-2012-110629
Julien C, Tremblay C, Émond V, Lebbadi M, Salem N, Bennett DA, et al. Sirtuin 1 reduction parallels the Accumulation of tau in Alzheimer Disease. J Neuropathology Experimental Neurol. 2009;68(1):48–58.
doi: 10.1097/NEN.0b013e3181922348
Cunnane SC, Chouinard-Watkins R, Castellano CA, Barberger-Gateau P. Docosahexaenoic acid homeostasis, brain aging and Alzheimer’s disease: can we reconcile the evidence? Prostaglandins Leukot Essent Fat Acids. 2013;88(1):61–70.
doi: 10.1016/j.plefa.2012.04.006
Bousquet M, Saint-Pierre M, Julien C, Salem N, Cicchetti F, Calon F. Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson’s disease. FASEB J. 2008;22(4):1213–25.
pubmed: 18032633
doi: 10.1096/fj.07-9677com
Bousquet M, Gibrat C, Saint-Pierre M, Julien C, Calon F, Cicchetti F. Modulation of brain-derived neurotrophic factor as a potential neuroprotective mechanism of action of omega-3 fatty acids in a parkinsonian animal model. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(8):1401–8.
pubmed: 19632286
doi: 10.1016/j.pnpbp.2009.07.018
Calon F, Cicchetti F. Can we prevent Parkinson’s disease with n-3 polyunsaturated fatty acids? Future Lipidol - FUTURE LIPIDOL. 2008;3:133–7.
doi: 10.2217/17460875.3.2.133
Coulombe K, Saint-Pierre M, Cisbani G, St-Amour I, Gibrat C, Giguère-Rancourt A, et al. Partial neurorescue effects of DHA following a 6-OHDA lesion of the mouse dopaminergic system. J Nutr Biochem. 2016;30:133–42.
pubmed: 27012630
doi: 10.1016/j.jnutbio.2015.11.014
Louis ED. Essential tremor and the cerebellum. Handb Clin Neurol. 2018;155:245–58.
pubmed: 29891062
doi: 10.1016/B978-0-444-64189-2.00016-0
Louis ED, Huang, CC, Dyke JP, Long Z, Dydak U. Neuroimaging studies of essential tremor: how well do these studies support/refute the neurodegenerative hypothesis? Tremor Other Hyperkinet Mov (N Y). 2014;4(235).
Babij R, Lee M, Cortés E, Vonsattel JP, Faust PL, Louis ED. Purkinje cell axonal anatomy: quantifying morphometric changes in essential tremor versus control brains. Brain. 2013;136(Pt 10):3051–61.
pubmed: 24030953
pmcid: 3784286
doi: 10.1093/brain/awt238
Paris-Robidas S, Brochu E, Sintes M, Emond V, Bousquet M, Vandal M, et al. Defective dentate nucleus GABA receptors in essential tremor. Brain. 2012;135(Pt 1):105–16.
pubmed: 22120148
doi: 10.1093/brain/awr301
Béliveau E, Tremblay C, Aubry-Lafontaine É, Paris-Robidas S, Delay C, Robinson C, et al. Accumulation of amyloid-β in the cerebellar cortex of essential tremor patients. Neurobiol Dis. 2015;82:397–408.
pubmed: 26253607
doi: 10.1016/j.nbd.2015.07.016
Zhang X, Santaniello S. Role of cerebellar GABAergic dysfunctions in the origins of essential tremor. Proc Natl Acad Sci U S A. 2019;116(27):13592–601.
pubmed: 31209041
pmcid: 6612915
doi: 10.1073/pnas.1817689116
Martuscello RT, Chen ML, Reiken S, Sittenfeld LR, Ruff DS, Ni CL, et al. Defective cerebellar ryanodine receptor type 1 and endoplasmic reticulum calcium ‘leak’ in tremor pathophysiology. Acta Neuropathol. 2023;146(2):301–18.
pubmed: 37335342
pmcid: 10350926
doi: 10.1007/s00401-023-02602-z
Delay C, Tremblay C, Brochu E, Paris-Robidas S, Emond V, Rajput AH, et al. Increased LINGO1 in the cerebellum of essential tremor patients. Mov Disord. 2014;29(13):1637–47.
pubmed: 24531928
doi: 10.1002/mds.25819
Kuo SH, Tang G, Louis ED, Ma K, Babji R, Balatbat M, et al. Lingo-1 expression is increased in essential tremor cerebellum and is present in the basket cell pinceau. Acta Neuropathol. 2013;125(6):879–89.
pubmed: 23543187
pmcid: 3663903
doi: 10.1007/s00401-013-1108-7
Shill HA, Adler CH, Sabbagh MN, Connor DJ, Caviness JN, Hentz JG, et al. Pathologic findings in prospectively ascertained essential tremor subjects. Neurology. 2008;70(16 Pt 2):1452–5.
pubmed: 18413570
doi: 10.1212/01.wnl.0000310425.76205.02
Rajput AH, Robinson CA, Rajput ML, Robinson SL, Rajput A. Essential tremor is not dependent upon cerebellar Purkinje cell loss. Parkinsonism Relat Disord. 2012;18(5):626–8.
pubmed: 22306459
doi: 10.1016/j.parkreldis.2012.01.013
Ibrahim MF, Beevis JC, Empson RM, Essential. Tremor - Cerebellar Driven Disorder? Neurosci. 2021;462:262–73.
Lieb J, Horrobin DF. Treatment of lithium-induced tremor and familial essential tremor with essential fatty acids. Prog Lipid Res. 1981;20:535–7.
pubmed: 7342107
doi: 10.1016/0163-7827(81)90094-1
Voller B, Lines E, McCrossin G, Tinaz S, Lungu C, Grimes G, et al. Dose-escalation study of octanoic acid in patients with essential tremor. J Clin Invest. 2016;126(4):1451–7.
pubmed: 26927672
pmcid: 4811161
doi: 10.1172/JCI83621
Scarmeas N, Louis ED. Mediterranean diet and essential tremor. A case-control study. Neuroepidemiology. 2007;29(3–4):170–7.
pubmed: 18043001
doi: 10.1159/000111579
Svennerholm L. Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res. 1968;9(5):570–9.
pubmed: 4302302
doi: 10.1016/S0022-2275(20)42702-6
Martínez M, Mougan I. Fatty acid composition of human brain phospholipids during normal development. J Neurochem. 1998;71(6):2528–33.
pubmed: 9832152
doi: 10.1046/j.1471-4159.1998.71062528.x
Rajput A, Robinson CA, Rajput AH. Essential tremor course and disability: a clinicopathologic study of 20 cases. Neurology. 2004;62(6):932–6.
pubmed: 15037695
doi: 10.1212/01.WNL.0000115145.18830.1A
Julien C, Tremblay C, Bendjelloul F, Phivilay A, Coulombe MA, Emond V, et al. Decreased drebrin mRNA expression in Alzheimer disease: correlation with tau pathology. J Neurosci Res. 2008;86(10):2292–302.
pubmed: 18338803
doi: 10.1002/jnr.21667
Julien C, Tremblay C, Emond V, Lebbadi M, Salem N, Bennett DA, et al. Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer disease. J Neuropathol Exp Neurol. 2009;68(1):48–58.
pubmed: 19104446
doi: 10.1097/NEN.0b013e3181922348
Shaikh NA, Downar E. Time course of changes in porcine myocardial phospholipid levels during ischemia. A reassessment of the lysolipid hypothesis. Circ Res. 1981;49(2):316–25.
pubmed: 7249269
doi: 10.1161/01.RES.49.2.316
Shaikh NA. Extraction, purification, and analysis of lipids from animal tissues. New York: Raven; 1986.
Lepage G, Roy CC. Direct transesterification of all classes of lipids in a one-step reaction. J Lipid Res. 1986;27(1):114–20.
pubmed: 3958609
doi: 10.1016/S0022-2275(20)38861-1
Da Silva MS, Julien P, Pérusse L, Vohl MC, Rudkowska I. Natural rumen-derived trans fatty acids are Associated with metabolic markers of Cardiac Health. Lipids. 2015;50(9):873–82.
pubmed: 26210489
doi: 10.1007/s11745-015-4055-3
Tremblay C, St-Amour I, Schneider J, Bennett DA, Calon F. Accumulation of transactive response DNA binding protein 43 in mild cognitive impairment and Alzheimer disease. J Neuropathol Exp Neurol. 2011;70(9):788–98.
pubmed: 21865887
doi: 10.1097/NEN.0b013e31822c62cf
Sun GY, Chuang DY, Zong Y, Jiang J, Lee JC, Gu Z, et al. Role of cytosolic phospholipase A2 in oxidative and inflammatory signaling pathways in different cell types in the central nervous system. Mol Neurobiol. 2014;50(1):6–14.
pubmed: 24573693
pmcid: 4147031
doi: 10.1007/s12035-014-8662-4
Rosenberger TA, Villacreses NE, Contreras MA, Bonventre JV, Rapoport SI. Brain lipid metabolism in the cPLA2 knockout mouse. J Lipid Res. 2003;44(1):109–17.
pubmed: 12518029
doi: 10.1194/jlr.M200298-JLR200
Farooqui AA, Horrocks LA. Phospholipase A2-generated lipid mediators in the brain: the good, the bad, and the ugly. Neuroscientist. 2006;12(3):245–60.
pubmed: 16684969
doi: 10.1177/1073858405285923
Farooqui AA, Ong WY, Horrocks LA. Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev. 2006;58(3):591–620.
pubmed: 16968951
doi: 10.1124/pr.58.3.7
Horrobin DF, Manku MS, Hillman H, Iain A, Glen M. Fatty acid levels in the brains of schizophrenics and normal controls. Biol Psychiatry. 1991;30(8):795–805.
pubmed: 1751622
doi: 10.1016/0006-3223(91)90235-E
Eder K, Kish SJ, Kirchgessner M, Ross BM. Brain phospholipids and fatty acids in Friedreich’s ataxia and spinocerebellar atrophy type-1. Mov Disord. 1998;13(5):813–9.
pubmed: 9756151
doi: 10.1002/mds.870130510
Jeon K. International Review of Cell and Molecular Biology. Academic; 2016. p. 368.
Vance JE. Phosphatidylserine and phosphatidylethanolamine in mammalian cells: two metabolically related aminophospholipids. J Lipid Res. 2008;49(7):1377–87.
pubmed: 18204094
doi: 10.1194/jlr.R700020-JLR200
Freysz L, Bieth R, Judes C, Sensenbrenner J, Jacob M, Mandel P. [Quantitative distribution of phospholipids in neurons and glial cells isolated from rat cerebral cortex]. J Neurochem. 1968;15(4):307–13.
pubmed: 4295964
doi: 10.1111/j.1471-4159.1968.tb11615.x
Norton WT, Poduslo SE. Neuronal perikarya and astroglia of rat brain: chemical composition during myelination. J Lipid Res. 1971;12(1):84–90.
pubmed: 5542708
doi: 10.1016/S0022-2275(20)39550-X
Ansell GB, Spanner S. Functional metabolism of brain phospholipids. Int Rev Neurobiol. 1977;20:1–29.
pubmed: 22508
doi: 10.1016/S0074-7742(08)60649-2
Hamberger A, Svennerholm L. Composition of gangliosides and phospholipids of neuronal and glial cell enriched fractions. J Neurochem. 1971;18(10):1821–9.
pubmed: 5118336
doi: 10.1111/j.1471-4159.1971.tb09587.x
Calzada E, Onguka O, Claypool SM. Phosphatidylethanolamine Metabolism in Health and Disease. Int Rev Cell Mol Biol. 2016;321:29–88.
pubmed: 26811286
doi: 10.1016/bs.ircmb.2015.10.001
Pettegrew JW, Panchalingam K, Hamilton RL, McClure RJ. Brain membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res. 2001;26(7):771–82.
pubmed: 11565608
doi: 10.1023/A:1011603916962
Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR. Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res. 1998;23(1):81–8.
pubmed: 9482271
doi: 10.1023/A:1022457605436
Vasquez J, Roldan E. Phospholipid metabolism in boar spermatozoa and role of diacylglycerol species in the De Novo formation of phosphatidylcholine. Mol Reprod Dev. 1997;47.
Hermansson M, Hokynar K, Somerharju P. Mechanisms of glycerophospholipid homeostasis in mammalian cells. Prog Lipid Res. 2011;50(3):240–57.
pubmed: 21382416
doi: 10.1016/j.plipres.2011.02.004
Horibata Y, Hirabayashi Y. Identification and characterization of human ethanolaminephosphotransferase1. J Lipid Res. 2007;48(3):503–8.
pubmed: 17132865
doi: 10.1194/jlr.C600019-JLR200
van Meer G, Voelker DR, Feigenson GW. Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008;9(2):112–24.
pubmed: 18216768
pmcid: 2642958
doi: 10.1038/nrm2330
Rodriguez-Cueto C, Benito C, Fernandez-Ruiz J, Romero J, Hernandez-Galvez M, Gomez-Ruiz M. Changes in CB(1) and CB(2) receptors in the post-mortem cerebellum of humans affected by spinocerebellar ataxias. Br J Pharmacol. 2014;171(6):1472–89.
pubmed: 23808969
pmcid: 3954486
doi: 10.1111/bph.12283
Carlsen EMM, Falk S, Skupio U, Robin L, Pagano Zottola AC, Marsicano G, et al. Spinal astroglial cannabinoid receptors control pathological tremor. Nat Neurosci. 2021;24(5):658–66.
pubmed: 33737752
pmcid: 7610740
doi: 10.1038/s41593-021-00818-4
Samuelsson B, Dahlen SE, Lindgren JA, Rouzer CA, Serhan CN. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987;237(4819):1171–6.
pubmed: 2820055
doi: 10.1126/science.2820055
Yan M, Zhang S, Li C, Liu Y, Zhao J, Wang Y, et al. 5-Lipoxygenase as an emerging target against age-related brain disorders. Ageing Res Rev. 2021;69:101359.
pubmed: 33984528
doi: 10.1016/j.arr.2021.101359
Barbosa-Silva MC, RM PC, Del Castilo I, Franca JV, Frost PS, Penido C, et al. Mice lacking 5-lipoxygenase display motor deficits associated with cortical and hippocampal synapse abnormalities. Brain Behav Immun. 2022;100:183–93.
pubmed: 34896181
doi: 10.1016/j.bbi.2021.12.004
Iversen L, Fogh K, Bojesen G, Kragballe K. Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophils in vitro. Evidence of formation of antiinflammatory compounds. Agents Actions. 1991;33(3–4):286–91.
pubmed: 1659156
doi: 10.1007/BF01986575
Rajan S, Jang Y, Kim CH, Kim W, Toh HT, Jeon J et al. PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function. Nat Chem Biol. 2020.
Bartels AL, Leenders KL. Cyclooxygenase and neuroinflammation in Parkinson’s disease neurodegeneration. Curr Neuropharmacol. 2010;8(1):62–8.
pubmed: 20808546
pmcid: 2866462
doi: 10.2174/157015910790909485
Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004;63(9):901–10.
pubmed: 15453089
doi: 10.1093/jnen/63.9.901
Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science. 2001;294(5548):1871–5.
pubmed: 11729303
doi: 10.1126/science.294.5548.1871
Fabelo N, Martin V, Santpere G, Marin R, Torrent L, Ferrer I, et al. Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Med. 2011;17(9–10):1107–18.
pubmed: 21717034
pmcid: 3188884
doi: 10.2119/molmed.2011.00119
Ross BM, Mamalias N, Moszczynska A, Rajput AH, Kish SJ. Elevated activity of phospholipid biosynthetic enzymes in substantia nigra of patients with Parkinson’s disease. Neuroscience. 2001;102(4):899–904.
pubmed: 11182251
doi: 10.1016/S0306-4522(00)00501-7
Leventis PA, Grinstein S. The distribution and function of phosphatidylserine in cellular membranes. Annu Rev Biophys. 2010;39:407–27.
pubmed: 20192774
doi: 10.1146/annurev.biophys.093008.131234
Kubo S, Nemani VM, Chalkley RJ, Anthony MD, Hattori N, Mizuno Y, et al. A combinatorial code for the interaction of alpha-synuclein with membranes. J Biol Chem. 2005;280(36):31664–72.
pubmed: 16020543
doi: 10.1074/jbc.M504894200
Davidson WS, Jonas A, Clayton DF, George JM. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 1998;273(16):9443–9.
pubmed: 9545270
doi: 10.1074/jbc.273.16.9443
Perrin RJ, Woods WS, Clayton DF, George JM. Interaction of human alpha-synuclein and Parkinson’s disease variants with phospholipids. Structural analysis using site-directed mutagenesis. J Biol Chem. 2000;275(44):34393–8.
pubmed: 10952980
doi: 10.1074/jbc.M004851200
de Lau LM, Bornebroek M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. Neurology. 2005;64(12):2040–5.
pubmed: 15985568
doi: 10.1212/01.WNL.0000166038.67153.9F
Kerdiles O, Oye Mintsa Mi-Mba MF, Coulombe K, Tremblay C, Émond V, et al. Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease. Neural Regen Res. 2025;20(2):574–586.
Fecchio C, Palazzi L, de Laureto PP. α-Synuclein and polyunsaturated fatty acids: molecular basis of the Interaction and Implication in Neurodegeneration. Molecules. 2018;23(7).
Fanning S, Selkoe D, Dettmer U. Parkinson’s disease: proteinopathy or lipidopathy? Npj Parkinson’s Disease. 2020;6:3.
pubmed: 31909184
pmcid: 6941970
doi: 10.1038/s41531-019-0103-7
Gardener H, Caunca MR. Mediterranean Diet in preventing neurodegenerative diseases. Curr Nutr Rep. 2018;7(1):10–20.
pubmed: 29892785
pmcid: 7212497
doi: 10.1007/s13668-018-0222-5
Arevalo-Rodriguez I, Smailagic N, Roqué i Figuls M, Ciapponi A, Sanchez‐Perez E, Giannakou A et al. Mini‐Mental State Examination (MMSE) for the detection of Alzheimer’s disease and other dementias in people with mild cognitive impairment (MCI). Cochrane Database Syst Reviews. 2015(3).
Fonteh AN, Cipolla M, Chiang J, Arakaki X, Harrington MG. Human cerebrospinal fluid fatty acid levels differ between supernatant fluid and brain-derived nanoparticle fractions, and are altered in Alzheimer’s disease. PLoS ONE. 2014;9(6):e100519.
pubmed: 24956173
pmcid: 4067345
doi: 10.1371/journal.pone.0100519
Park M, Ross G, Petrovitch H, White L, Masaki K, Nelson J, et al. Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Neurology. 2005;64:1047–51.
pubmed: 15781824
doi: 10.1212/01.WNL.0000154532.98495.BF
Chen H, O’Reilly E, McCullough M, Rodriguez C, Schwarzschild M, Calle E, et al. Consumption of dairy products and risk of Parkinson’s Disease. Am J Epidemiol. 2007;165:998–1006.
pubmed: 17272289
doi: 10.1093/aje/kwk089
Anderson C, Checkoway H, Franklin GM, Beresford S, Smith-Weller T, Swanson PD. Dietary factors in Parkinson’s disease: the role of food groups and specific foods. Mov Disord. 1999;14(1):21–7.
pubmed: 9918340
doi: 10.1002/1531-8257(199901)14:1<21::AID-MDS1006>3.0.CO;2-Y
Mischley LK, Lau RC, Bennett RD. Role of Diet and Nutritional supplements in Parkinson’s Disease Progression. Oxid Med Cell Longev. 2017;2017:6405278.
pubmed: 29081890
pmcid: 5610862
doi: 10.1155/2017/6405278
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(5):3810–3819
Rouser G, Yamamoto A. Curvilinear regression course of human brain lipid composition changes with age. Lipids. 1968;3(3):284–7.
pubmed: 17805871
doi: 10.1007/BF02531202
Shichiri M, Yoshida Y, Niki E. Chapter 4 - unregulated lipid peroxidation in neurological dysfunction. In: Watson RR, De Meester F, editors. Omega-3 fatty acids in Brain and Neurological Health. Boston: Academic; 2014. pp. 31–55.
Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018;13:757–72.
pubmed: 29731617
pmcid: 5927356
doi: 10.2147/CIA.S158513
Svennerholm L, Boström K, Helander CG, Jungbjer B. Membrane lipids in the aging human brain. J Neurochem. 1991;56(6):2051–9.
pubmed: 2027013
doi: 10.1111/j.1471-4159.1991.tb03466.x
Svennerholm L, Boström K, Jungbjer B, Olsson L. Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J Neurochem. 1994;63(5):1802–11.
pubmed: 7931336
doi: 10.1046/j.1471-4159.1994.63051802.x
Farooqui AA, Liss L, Horrocks LA. Neurochemical aspects of Alzheimer’s disease: involvement of membrane phospholipids. Metab Brain Dis. 1988;3(1):19–35.
pubmed: 3062351
doi: 10.1007/BF01001351
Stöckl M, Fischer P, Wanker E, Herrmann A. Alpha-synuclein selectively binds to anionic phospholipids embedded in liquid-disordered domains. J Mol Biol. 2008;375(5):1394–404.
pubmed: 18082181
doi: 10.1016/j.jmb.2007.11.051
Abd-Elhadi S, Basora M, Vilas D, Tolosa E, Sharon R. Total α-synuclein levels in human blood cells, CSF, and saliva determined by a lipid-ELISA. Anal Bioanal Chem. 2016;408(27):7669–77.
pubmed: 27624766
doi: 10.1007/s00216-016-9863-7
Iyer A, Claessens MMAE. Disruptive membrane interactions of alpha-synuclein aggregates. Biochim Biophys Acta Proteins Proteom. 2019;1867(5):468–82.
pubmed: 30315896
doi: 10.1016/j.bbapap.2018.10.006
Fecchio C, De Franceschi G, Relini A, Greggio E, Dalla Serra M, Bubacco L, et al. α-Synuclein oligomers induced by docosahexaenoic acid affect membrane integrity. PLoS ONE. 2013;8(11):e82732.
pubmed: 24312431
pmcid: 3843715
doi: 10.1371/journal.pone.0082732
De Franceschi G, Frare E, Pivato M, Relini A, Penco A, Greggio E, et al. Structural and morphological characterization of aggregated species of α-synuclein induced by docosahexaenoic acid. J Biol Chem. 2011;286(25):22262–74.
pubmed: 21527634
pmcid: 3121372
doi: 10.1074/jbc.M110.202937
Snead D, Eliezer D. Alpha-synuclein function and dysfunction on cellular membranes. Exp Neurobiol. 2014;23(4):292–313.
pubmed: 25548530
pmcid: 4276801
doi: 10.5607/en.2014.23.4.292
Chandra S, Chen X, Rizo J, Jahn R, Südhof TC. A broken alpha -helix in folded alpha -synuclein. J Biol Chem. 2003;278(17):15313–8.
pubmed: 12586824
doi: 10.1074/jbc.M213128200
Sharon R, Bar-Joseph I, Frosch MP, Walsh DM, Hamilton JA, Selkoe DJ. The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson’s disease. Neuron. 2003;37(4):583–95.
pubmed: 12597857
doi: 10.1016/S0896-6273(03)00024-2
Emamzadeh FN. Alpha-synuclein structure, functions, and interactions. J Res Med Sci. 2016;21:29.
pubmed: 27904575
pmcid: 5122110
doi: 10.4103/1735-1995.181989
Matveyenka M, Zhaliazka K, Kurouski D. Unsaturated fatty acids uniquely alter aggregation rate of alpha-synuclein and insulin and change the secondary structure and toxicity of amyloid aggregates formed in their presence. FASEB Journal: Official Publication Federation Am Soc Experimental Biology. 2023;37(7):e22972.
doi: 10.1096/fj.202300003R
Coulombe K, Kerdiles O, Tremblay C, Emond V, Lebel M, Boulianne AS, et al. Impact of DHA intake in a mouse model of synucleinopathy. Exp Neurol. 2018;301(Pt A):39–49.
pubmed: 29229294
doi: 10.1016/j.expneurol.2017.12.002
Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015;7:52.
pubmed: 25954194
pmcid: 4404917
doi: 10.3389/fnagi.2015.00052
Seidl SE, Santiago JA, Bilyk H, Potashkin JA. The emerging role of nutrition in Parkinson’s disease. Front Aging Neurosci. 2014;6:36.
pubmed: 24639650
pmcid: 3945400
doi: 10.3389/fnagi.2014.00036
Gonzalez-Riano C, Tapia-González S, García A, Muñoz A, DeFelipe J, Barbas C. Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus. Brain Struct Funct. 2017;222(6):2831–53.
pubmed: 28285370
pmcid: 5541081
doi: 10.1007/s00429-017-1375-5
Zurier RB, Quagliata F. Effect of prostaglandin E 1 on adjuvant arthritis. Nature. 1971;234(5327):304–5.
pubmed: 5003042
doi: 10.1038/234304a0