Omega-3 Fatty Acids as Druggable Therapeutics for Neurodegenerative Disorders

Author(s): Neha M. Chitre, Nader H. Moniri, Kevin S. Murnane*.

Journal Name: CNS & Neurological Disorders - Drug Targets
(Formerly Current Drug Targets - CNS & Neurological Disorders)

Volume 18 , Issue 10 , 2019

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Abstract:

Neurodegenerative disorders are commonly associated with a complex pattern of pathophysiological hallmarks, including increased oxidative stress and neuroinflammation, which makes their treatment challenging. Omega-3 Fatty Acids (O3FA) are natural products with reported neuroprotective, anti-inflammatory, and antioxidant effects. These effects have been attributed to their incorporation into neuronal membranes or through the activation of intracellular or recently discovered cell-surface receptors (i.e., Free-Fatty Acid Receptors; FFAR). Molecular docking studies have investigated the roles of O3FA as agonists of FFAR and have led to the development of receptor-specific targeted agonists for therapeutic purposes. Moreover, novel formulation strategies for targeted delivery of O3FA to the brain have supported their development as therapeutics for neurodegenerative disorders. Despite the compelling evidence of the beneficial effects of O3FA for several neuroprotective functions, they are currently only available as unregulated dietary supplements, with only a single FDA-approved prescription product, indicated for triglyceride reduction. This review highlights the relative safety and efficacy of O3FA, their drug-like properties, and their capacity to be formulated in clinically viable drug delivery systems. Interestingly, the presence of cardiac conditions such as hypertriglyceridemia is associated with brain pathophysiological hallmarks of neurodegeneration, such as neuroinflammation, thereby further suggesting potential therapeutic roles of O3FA for neurodegenerative disorders. Taken together, this review article summarizes and integrates the compelling evidence regarding the feasibility of developing O3FA and their synthetic derivatives as potential drugs for neurodegenerative disorders.

Keywords: Omega-3 fatty acids, neurodegenerative disorders, prescription therapies, free fatty acid receptor, synthetic agonists, intracellular signaling.

[1]
Baune BT. Inflammation and neurodegenerative disorders: Is there still hope for therapeutic intervention? Curr Opin Psychiatry 2015; 28(2): 148-54.
[http://dx.doi.org/10.1097/YCO.0000000000000140] [PMID: 25602246]
[2]
Bhat AH, Dar KB, Anees S, et al. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 2015; 74: 101-10.
[3]
Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases. (Review). Mol Med Rep 2016; 13(4): 3391-6.
[http://dx.doi.org/ [http://10.3892/mmr.2016.4948] [PMID: 26935478]
[4]
Lindsey LP, Daphney CM, Oppong-Damoah A, et al. The cannabinoid receptor 2 agonist, β-caryophyllene, improves working memory and reduces circulating levels of specific proinflammatory cytokines in aged male mice. Behav Brain Res 2019; 372: : 112012..
[http://dx.doi.org/10.1016/j.bbr.2019.112012] [PMID: 31173795]
[5]
Botchway BOA, Moore MK, Akinleye FO, Iyer IC, Fang M. Nutrition: Review on the possible treatment for Alzheimer’s disease. J Alzheimers Dis 2018; 61(3): 867-83.
[http://dx.doi.org/10.3233/JAD-170874] [PMID: 29254101]
[6]
Bui TT, Nguyen TH. Natural product for the treatment of Alzheimer’s disease. J Basic Clin Physiol Pharmacol 2017; 28(5): 413-23.
[http://dx.doi.org/10.1515/jbcpp-2016-0147] [PMID: 28708573]
[7]
Solayman M, Islam MA, Alam F, Khalil MI, Kamal MA, Gan SH. Natural products combating neurodegeneration: Parkinson’s disease. Curr Drug Metab 2017; 18(1): 50-61.
[http://dx.doi.org/10.2174/1389200217666160709204826] [PMID: 27396919]
[8]
Parvez MK. Natural or plant products for the treatment of neurological disorders: Current knowledge. Curr Drug Metab 2018; 19(5): 424-8.
[http://dx.doi.org/10.2174/1389200218666170710190249] [PMID: 28699506]
[9]
Layé S, Nadjar A, Joffre C, Bazinet RP. Anti-inflammatory effects of omega-3 fatty acids in the brain: Physiological mechanisms and relevance to pharmacology. Pharmacol Rev 2018; 70(1): 12-38.
[http://dx.doi.org/10.1124/pr.117.014092] [PMID: 29217656]
[10]
Calder PC. Mechanisms of action of (n-3) fatty acids. J Nutr 2012; 142(3): 592S-9S.
[http://dx.doi.org/10.3945/jn.111.155259] [PMID: 22279140]
[11]
Echeverría F, Valenzuela R, Catalina Hernandez-Rodas M, Valenzuela A. Docosahexaenoic Acid (DHA), a fundamental fatty acid for the brain: New dietary sources. Prostaglandins Leukot Essent Fatty Acids 2017; 124: 1-10.
[http://dx.doi.org/10.1016/j.plefa.2017.08.001] [PMID: 28870371]
[12]
Bazinet RP, Layé S. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nat Rev Neurosci 2014; 15(12): 771-85.
[http://dx.doi.org/10.1038/nrn3820] [PMID: 25387473]
[13]
Clifford JJ, Drago J, Natoli AL, et al. Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington’s disease. Neuroscience 2002; 109(1): 81-8.
[http://dx.doi.org/10.1016/S0306-4522(01)00409-2] [PMID: 11784701]
[14]
Barros AS, Crispim RYG, Cavalcanti JU, et al. Impact of the chronic omega-3 fatty acids supplementation in hemiparkinsonism model induced by 6-hydroxydopamine in rats. Basic Clin Pharmacol Toxicol 2017; 120(6): 523-31.
[http://dx.doi.org/10.1111/bcpt.12713] [PMID: 27883274]
[15]
Grimm MOW, Michaelson DM, Hartmann T. Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer’s disease: A rationale for multi-nutrient dementia prevention. J Lipid Res 2017; 58(11): 2083-101.
[http://dx.doi.org/10.1194/jlr.R076331] [PMID: 28528321]
[16]
Olivera-Perez HM, Lam L, Dang J, et al. Omega-3 fatty acids increase the unfolded protein response and improve amyloid-β phagocytosis by macrophages of patients with mild cognitive impairment. FASEB J 2017; 31(10): 4359-69.
[http://dx.doi.org/10.1096/fj.201700290R] [PMID: 28634213]
[17]
Deacon G, Kettle C, Hayes D, Dennis C, Tucci J. Omega 3 polyunsaturated fatty acids and the treatment of depression. Crit Rev Food Sci Nutr 2017; 57(1): 212-23.
[http://dx.doi.org/10.1080/10408398.2013.876959] [PMID: 25830700]
[18]
Grosso G, Pajak A, Marventano S, et al. Role of omega-3 fatty acids in the treatment of depressive disorders: A comprehensive meta-analysis of randomized clinical trials. PLoS One 2014; 9(5): e96905.
[http://dx.doi.org/10.1371/journal.pone.0096905] [PMID: 24805797]
[19]
Behdani F, Roudbaraki SN, Saberi-Karimian M, et al. Assessment of the efficacy of omega-3 fatty acids on metabolic and inflammatory parameters in patients with schizophrenia taking clozapine and sodium valproate. Psychiatry Res 2018; 261: 243-7.
[http://dx.doi.org/10.1016/j.psychres.2017.12.028] [PMID: 29329042]
[20]
Heemels MT. Neurodegenerative diseases. Nature 2016; 539(7628): 179.
[http://dx.doi.org/10.1038/539179a] [PMID: 27830810]
[21]
Kovacs GG. Concepts and classification of neurodegenerative diseases. Handb Clin Neurol 2017; 145: 301-7.
[http://dx.doi.org/10.1016/B978-0-12-802395-2.00021-3] [PMID: 28987178]
[22]
Dugger BN, Dickson DW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol 2017; 9(7): a028035.
[http://dx.doi.org/10.1101/cshperspect.a028035] [PMID: 28062563]
[23]
Jeromin A, Bowser R. Biomarkers in Neurodegenerative Diseases. Adv Neurobiol 2017; 15: 491-528.
[http://dx.doi.org/10.1007/978-3-319-57193-5_20] [PMID: 28674995]
[24]
Joshi N, Singh S. Updates on immunity and inflammation in Parkinson disease pathology. J Neurosci Res 2018; 96(3): 379-90.
[http://dx.doi.org/10.1002/jnr.24185] [PMID: 29072332]
[25]
Cerami C, Iaccarino L, Perani D. Molecular Imaging of neuroinflammation in neurodegenerative dementias: The role of in vivo PET imaging. Int J Mol Sci 2017; 18(5): E993.
[http://dx.doi.org/10.3390/ijms18050993] [PMID: 28475165]
[26]
Singh A, Chokriwal A, Sharma MM, Jain D, Saxena J, Stephen BJ. Therapeutic role and drug delivery potential of neuroinflammation as a target in neurodegenerative disorders. ACS Chem Neurosci 2017; 8(8): 1645-55.
[http://dx.doi.org/10.1021/acschemneuro.7b00144] [PMID: 28719178]
[27]
Amor S, Peferoen LA, Vogel DY, et al. Inflammation in neurodegenerative diseases--an update. Immunology 2014; 142(2): 151-66.
[http://dx.doi.org/10.1111/imm.12233] [PMID: 24329535]
[28]
Zhang W, Wang T, Pei Z, et al. Aggregated alpha-synuclein activates microglia: A process leading to disease progression in Parkinson’s disease. FASEB J 2005; 19(6): 533-42.
[http://dx.doi.org/10.1096/fj.04-2751com] [PMID: 15791003]
[29]
Koprich JB, Reske-Nielsen C, Mithal P, Isacson O. Neuroinflammation mediated by IL-1 beta increases susceptibility of dopamine neurons to degeneration in an animal model of Parkinson’s disease. J Neuroinflammation 2008; 5: 8.
[http://dx.doi.org/10.1186/1742-2094-5-8] [PMID: 18304357]
[30]
Schain M, Kreisl WC. Neuroinflammation in neurodegenerative disorders-a review. Curr Neurol Neurosci Rep 2017; 17(3): 25.
[http://dx.doi.org/10.1007/s11910-017-0733-2] [PMID: 28283959]
[31]
de Farias CC, Maes M, Bonifacio KL, et al. Parkinson’s disease is accompanied by intertwined alterations in iron metabolism and activated immune-inflammatory and oxidative stress pathways. CNS Neurol Disord Drug Targets 2017; 16(4): 484-91.
[http://dx.doi.org/10.2174/1871527316666170223161004] [PMID: 28240188]
[32]
Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 1996; 47(6)(Suppl. 3): S161-70.
[http://dx.doi.org/10.1212/WNL.47.6_Suppl_3.161S] [PMID: 8959985]
[33]
Islam MT. Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders. Neurol Res 2017; 39(1): 73-82.
[http://dx.doi.org/10.1080/01616412.2016.1251711] [PMID: 27809706]
[34]
Good PF, Werner P, Hsu A, Olanow CW, Perl DP. Evidence of neuronal oxidative damage in Alzheimer’s disease. Am J Pathol 1996; 149(1): 21-8.
[PMID: 8686745]
[35]
Hajjar I, Hayek SS, Goldstein FC, Martin G, Jones DP, Quyyumi A. Oxidative stress predicts cognitive decline with aging in healthy adults: An observational study. J Neuroinflammation 2018; 15(1): 17.
[http://dx.doi.org/10.1186/s12974-017-1026-z] [PMID: 29338747]
[36]
Yaribeygi H, Panahi Y, Javadi B, Sahebkar A. The underlying role of oxidative stress in neurodegeneration: A mechanistic review. CNS Neurol Disord Drug Targets 2018; 17(3): 207-15.
[http://dx.doi.org/10.2174/1871527317666180425122557] [PMID: 29692267]
[37]
Pamplona R, Dalfó E, Ayala V, et al. Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J Biol Chem 2005; 280(22): 21522-30.
[http://dx.doi.org/10.1074/jbc.M502255200] [PMID: 15799962]
[38]
Whitfield JF. Can statins put the brakes on Alzheimer’s disease? Expert Opin Investig Drugs 2006; 15(12): 1479-85.
[http://dx.doi.org/10.1517/13543784.15.12.1479] [PMID: 17107274]
[39]
Williams TI, Lynn BC, Markesbery WR, Lovell MA. Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in mild cognitive impairment and early Alzheimer’s disease. Neurobiol Aging 2006; 27(8): 1094-9.
[http://dx.doi.org/10.1016/j.neurobiolaging.2005.06.004] [PMID: 15993986]
[40]
Favrelère S, Stadelmann-Ingrand S, Huguet F, et al. Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus. Neurobiol Aging 2000; 21(5): 653-60.
[http://dx.doi.org/10.1016/S0197-4580(00)00170-6] [PMID: 11016534]
[41]
Chung W-L, Chen J-J, Su H-M. Fish oil supplementation of control and (n-3) fatty acid-deficient male rats enhances reference and working memory performance and increases brain regional docosahexaenoic acid levels. J Nutr 2008; 138(6): 1165-71.
[http://dx.doi.org/10.1093/jn/138.6.1165] [PMID: 18492851]
[42]
Tarasova TV, Lytkina OA, Roman AY, Bachurin SO, Ustyugov AA. The role of alpha-synuclein in the development of the dopaminergic neurons in the substantia nigra and ventral tegmental area. Dokl Biol Sci 2016; 466: 5-7.
[http://dx.doi.org/10.1134/S0012496616010117]
[43]
Dexter DT, Carter CJ, Wells FR, et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 1989; 52(2): 381-9.
[http://dx.doi.org/10.1111/j.1471-4159.1989.tb09133.x] [PMID: 2911023]
[44]
Ahmad SO, Park JH, Radel JD, Levant B. Reduced numbers of dopamine neurons in the substantia nigra pars compacta and ventral tegmental area of rats fed an n-3 polyunsaturated fatty acid-deficient diet: A stereological study. Neurosci Lett 2008; 438(3): 303-7.
[http://dx.doi.org/10.1016/j.neulet.2008.04.073] [PMID: 18499349]
[45]
Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. alpha-Linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem 1996; 66(4): 1582-91.
[http://dx.doi.org/10.1046/j.1471-4159.1996.66041582.x] [PMID: 8627314]
[46]
Delion S, Chalon S, Hérault J, Guilloteau D, Besnard JC, Durand G. Chronic dietary alpha-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 1994; 124(12): 2466-76.
[http://dx.doi.org/10.1093/jn/124.12.2466] [PMID: 16856329]
[47]
Kodas E, Vancassel S, Lejeune B, Guilloteau D, Chalon S. Reversibility of n-3 fatty acid deficiency-induced changes in dopaminergic neurotransmission in rats: Critical role of developmental stage. J Lipid Res 2002; 43(8): 1209-19.
[PMID: 12177165]
[48]
Costa AC, Joaquim HPG, Forlenza O, Talib LL, Gattaz WF. Plasma lipids metabolism in mild cognitive impairment and Alzheimer’s disease. World J Biol Psychiatry 2019; 20(3): 190-6.
[http://dx.doi.org/10.1080/15622975.2017.1369566]
[49]
Parletta N, Zarnowiecki D, Cho J, et al. People with schizophrenia and depression have a low omega-3 index. Prostaglandins Leukot Essent Fatty Acids 2016; 110: 42-7.
[http://dx.doi.org/10.1016/j.plefa.2016.05.007] [PMID: 27255642]
[50]
Joseph J, Cole G, Head E, Ingram D. Nutrition, brain aging, and neurodegeneration. J Neurosci 2009; 29(41): 12795-801.
[http://dx.doi.org/10.1523/JNEUROSCI.3520-09.2009] [PMID: 19828791]
[51]
Cameron A, Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Curr Opin Clin Nutr Metab Care 2002; 5(6): 631-43.
[http://dx.doi.org/10.1097/00075197-200211000-00005] [PMID: 12394638]
[52]
Pandareesh MD, Kandikattu HK, Razack S, et al. Nutrition and nutraceuticals in neuroinflammatory and brain metabolic stress: Implications for neurodegenerative disorders. CNS Neurol Disord Drug Targets 2018; 17(9): 680-8.
[http://dx.doi.org/10.2174/1871527317666180625104753] [PMID: 29938622]
[53]
Roy Sarkar S, Banerjee S. Gut microbiota in neurodegenerative disorders. J Neuroimmunol 2019; 328: 98-104.
[http://dx.doi.org/10.1016/j.jneuroim.2019.01.004] [PMID: 30658292]
[54]
Relja M. Pathophysiology and classification of neurodegenerative diseases. EJIFCC 2004; 15(3): 97-9.
[PMID: 29988912]
[55]
Liang S, Wu X, Jin F. Gut-brain psychology: Rethinking psychology from the microbiota-gut-brain axis. Front Integr Nuerosci 2018; 12: 33.
[http://dx.doi.org/10.3389/fnint.2018.00033] [PMID: 30271330]
[56]
Caballero-Villarraso J, Galvan A, Escribano BM, Tunez I. Interrelationships among gut microbiota and host: Paradigms, role in neurodegenerative diseases and future prospects. CNS Neurol Disord Drug Targets 2017; 16(8): 945-64.
[PMID: 28714393]
[57]
Tur JA, Bibiloni MM, Sureda A, Pons A. Dietary sources of omega 3 fatty acids: Public health risks and benefits. Br J Nutr 2012; 107(Suppl. 2): S23-52.
[http://dx.doi.org/10.1017/S0007114512001456] [PMID: 22591897]
[58]
Freitas HR, Ferreira GDC, Trevenzoli IH, Oliveira KJ, de Melo Reis RA. Fatty acids, antioxidants and physical activity in brain aging. Nutrients 2017; 9(11): E1263.
[http://dx.doi.org/10.3390/nu9111263] [PMID: 29156608]
[59]
Gustafson DR, Clare Morris M, Scarmeas N, et al. New Perspectives on Alzheimer’s disease and nutrition. J Alzheimers Dis 2015; 46(4): 1111-27.
[http://dx.doi.org/10.3233/JAD-150084] [PMID: 26402637]
[60]
Jenkins DJ, Josse AR. Fish oil and omega-3 fatty acids. CMAJ 2008; 178(2): 150.
[http://dx.doi.org/10.1503/cmaj.071754] [PMID: 18195286]
[61]
Belkouch M, Hachem M, Elgot A, et al. The pleiotropic effects of omega-3 docosahexaenoic acid on the hallmarks of Alzheimer’s disease. J Nutr Biochem 2016; 38: 1-11.
[http://dx.doi.org/10.1016/j.jnutbio.2016.03.002] [PMID: 27825512]
[62]
Denis I, Potier B, Heberden C, Vancassel S. Omega-3 polyunsaturated fatty acids and brain aging. Curr Opin Clin Nutr Metab Care 2015; 18(2): 139-46.
[http://dx.doi.org/10.1097/MCO.0000000000000141] [PMID: 25501348]
[63]
Wysoczański T, Sokoła-Wysoczańska E, Pękala J, et al. Omega-3 fatty acids and their role in central nervous system - a review. Curr Med Chem 2016; 23(8): 816-31.
[http://dx.doi.org/10.2174/0929867323666160122114439] [PMID: 26795198]
[64]
Tsagalioti E, Trifonos C, Morari A, Vadikolias K, Giaginis C. Clinical value of nutritional status in neurodegenerative diseases: What is its impact and how it affects disease progression and management? Nutr Neurosci 2018; 21(3): 162-75.
[http://dx.doi.org/10.1080/1028415X.2016.1261529] [PMID: 27900872]
[65]
Thomas J, Thomas CJ, Radcliffe J, Itsiopoulos C. Omega-3 fatty acids in early prevention of inflammatory neurodegenerative disease: A focus on Alzheimer’s disease. BioMed Res Int 2015; 2015: 172801.
[http://dx.doi.org/10.1155/2015/172801] [PMID: 26301243]
[66]
Oppong-Damoah A, Zaman RU, D’Souza MJ, Murnane KS. Nanoparticle encapsulation increases the brain penetrance and duration of action of intranasal oxytocin. Horm Behav 2019; 108: 20-9.
[http://dx.doi.org/10.1016/j.yhbeh.2018.12.011] [PMID: 30593782]
[67]
Billingsley ML. Druggable targets and targeted drugs: Enhancing the development of new therapeutics. Pharmacology 2008; 82(4): 239-44.
[http://dx.doi.org/10.1159/000157624] [PMID: 18802381]
[68]
Zaman RU, Mulla NS, Braz Gomes K, D’Souza C, Murnane KS, D’Souza MJ. Nanoparticle formulations that allow for sustained delivery and brain targeting of the neuropeptide oxytocin. Int J Pharm 2018; 548(1): 698-706.
[http://dx.doi.org/10.1016/j.ijpharm.2018.07.043] [PMID: 30031864]
[69]
Bagli E, Goussia A, Moschos MM, Agnantis N, Kitsos G. Natural compounds and neuroprotection: Mechanisms of action and novel delivery systems. In Vivo 2016; 30(5): 535-47.
[PMID: 27566070]
[70]
Cutuli D. Functional and structural benefits induced by omega-3 polyunsaturated fatty acids during aging. Curr Neuropharmacol 2017; 15(4): 534-42.
[http://dx.doi.org/10.2174/1570159X14666160614091311] [PMID: 27306037]
[71]
Ribeiro FF, Mendonca Junior F.J.B., Ghasemi JB, Ishiki HM, Scotti MT, Scotti L. Docking of natural products against neurodegenerative diseases: General concepts. Comb Chem High Throughput Screen 2018; 21(3): 152-60.
[http://dx.doi.org/10.2174/1386207321666180313130314] [PMID: 29532756]
[72]
Wu S, Ding Y, Wu F, Li R, Hou J, Mao P. Omega-3 fatty acids intake and risks of dementia and Alzheimer’s disease: A meta-analysis. Neurosci Biobehav Rev 2015; 48: 1-9.
[http://dx.doi.org/10.1016/j.neubiorev.2014.11.008] [PMID: 25446949]
[73]
Wang L, Fan H, He J, Wang L, Tian Z, Wang C. Protective effects of omega-3 fatty acids against Alzheimer’s disease in rat brain endothelial cells. Brain Behav 2018; 8(11): e01037.
[http://dx.doi.org/10.1002/brb3.1037] [PMID: 30298620]
[74]
Calon F, Cole G. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: Evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids 2007; 77(5-6): 287-93.
[http://dx.doi.org/10.1016/j.plefa.2007.10.019] [PMID: 18037281]
[75]
Delgado-Alvarado M, Gago B, Navalpotro-Gomez I, Jiménez-Urbieta H, Rodriguez-Oroz MC. Biomarkers for dementia and mild cognitive impairment in Parkinson’s disease. Mov Disord 2016; 31(6): 861-81.
[http://dx.doi.org/10.1002/mds.26662] [PMID: 27193487]
[76]
Jozwiak N, Postuma RB, Montplaisir J, et al. REM sleep behavior disorder and cognitive impairment in Parkinson’s disease. Sleep (Basel) 2017; 40(8)
[http://dx.doi.org/10.1093/sleep/zsx101] [PMID: 28645156]
[77]
Wang YX, Zhao J, Li DK, et al. Associations between cognitive impairment and motor dysfunction in Parkinson’s disease. Brain Behav 2017; 7(6): e00719.
[http://dx.doi.org/10.1002/brb3.719] [PMID: 28638722]
[78]
Zhang YP, Miao R, Li Q, Wu T, Ma F. Effects of DHA supplementation on hippocampal volume and cognitive function in older adults with mild cognitive impairment: A 12-month randomized, double-blind, placebo-controlled trial. J Alzheimers Dis 2017; 55(2): 497-507.
[http://dx.doi.org/10.3233/JAD-160439] [PMID: 27716665]
[79]
Shinto L, Quinn J, Montine T, et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and alpha lipoic acid in Alzheimer’s disease. J Alzheimers Dis 2014; 38(1): 111-20.
[http://dx.doi.org/10.3233/JAD-130722] [PMID: 24077434]
[80]
Kalmijn S, van Boxtel MP, Ocké M, Verschuren WM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology 2004; 62(2): 275-80.
[http://dx.doi.org/10.1212/01.WNL.0000103860.75218.A5] [PMID: 14745067]
[81]
Phillips MA, Childs CE, Calder PC, Rogers PJ. No effect of omega-3 fatty acid supplementation on cognition and mood in individuals with cognitive impairment and probable Alzheimer’s disease: A randomised controlled trial. Int J Mol Sci 2015; 16(10): 24600-13.
[http://dx.doi.org/10.3390/ijms161024600] [PMID: 26501267]
[82]
Cederholm T, Salem N Jr, Palmblad J. omega-3 fatty acids in the prevention of cognitive decline in humans. In: Advances in nutrition (Bethesda, Md) . 2013; 4: p. (6)672.
[83]
Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P. Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis. J Psychopharmacol (Oxford) 2015; 29(7): 753-63.
[http://dx.doi.org/10.1177/0269881115587958] [PMID: 26040902]
[84]
Canhada S, Castro K, Perry IS, Luft VC. Omega-3 fatty acids’ supplementation in Alzheimer’s disease: A systematic review. Nutr Neurosci 2018; 21(8): 529-38.
[http://dx.doi.org/10.1080/1028415X.2017.1321813] [PMID: 28466678]
[85]
Ajith TA. A recent update on the effects of omega-3 fatty acids in Alzheimer’s disease. Curr Clin Pharmacol 2018; 13(4): 252-60.
[http://dx.doi.org/10.2174/1574884713666180807145648] [PMID: 30084334]
[86]
Zhang Y, Chen J, Qiu J, Li Y, Wang J, Jiao J. Intakes of fish and polyunsaturated fatty acids and mild-to-severe cognitive impairment risks: A dose-response meta-analysis of 21 cohort studies. Am J Clin Nutr 2016; 103(2): 330-40.
[http://dx.doi.org/10.3945/ajcn.115.124081] [PMID: 26718417]
[87]
Burckhardt M, Herke M, Wustmann T, Watzke S, Langer G, Fink A. Omega-3 fatty acids for the treatment of dementia. Cochrane Database Syst Rev 2016; 4CD009002..
[http://dx.doi.org/10.1002/14651858.CD009002.pub3] [PMID: 27063583]
[88]
Quinn JF, Raman R, Thomas RG, et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: A randomized trial. JAMA 2010; 304(17): 1903-11.
[http://dx.doi.org/10.1001/jama.2010.1510] [PMID: 21045096]
[89]
Freund-Levi Y, Eriksdotter-Jönhagen M, Cederholm T, et al. Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: A randomized double-blind trial. Arch Neurol 2006; 63(10): 1402-8.
[http://dx.doi.org/10.1001/archneur.63.10.1402] [PMID: 17030655]
[90]
Mori MA, Delattre AM, Carabelli B, et al. Neuroprotective effect of omega-3 polyunsaturated fatty acids in the 6-OHDA model of Parkinson’s disease is mediated by a reduction of inducible nitric oxide synthase. Nutr Neurosci 2018; 21(5): 341-51.
[http://dx.doi.org/10.1080/1028415X.2017.1290928] [PMID: 28221817]
[91]
Mischley LK, Lau RC, Bennett RD. Role of diet and nutritional supplements in Parkinson’s disease progression. Oxidative medicine and cellular longevity 2017.
[http://dx.doi.org/10.1155/2017/6405278]
[92]
Afshordel S, Hagl S, Werner D, et al. Omega-3 polyunsaturated fatty acids improve mitochondrial dysfunction in brain aging--impact of Bcl-2 and NPD-1 like metabolites. Prostaglandins Leukot Essent Fatty Acids 2015; 92: 23-31.
[http://dx.doi.org/10.1016/j.plefa.2014.05.008] [PMID: 24972878]
[93]
Healy-Stoffel M, Levant B. N-3 (omega-3) fatty acids: Effects on brain dopamine systems and potential role in the etiology and treatment of neuropsychiatric disorders. CNS Neurol Disord Drug Targets 2018; 17(3): 216-32.
[http://dx.doi.org/10.2174/1871527317666180412153612] [PMID: 29651972]
[94]
Oppong-Damoah A, Curry KE, Blough BE, Rice KC, Murnane KS. Effects of the synthetic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) on ethanol consumption and place conditioning in male mice. Psychopharmacology (Berl) 2019; 236(12): 3567-78.
[http://dx.doi.org/10.1007/s00213-019-05328-7] [PMID: 31309240]
[95]
Oppong-Damoah A, Blough BE, Makriyannis A, Murnane KS. The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice. Heliyon 2019; 5(6): e01915.
[http://dx.doi.org/10.1016/j.heliyon.2019.e01915] [PMID: 31245644]
[96]
Hyatt WS, Berquist MD, Chitre NM, et al. Repeated administration of synthetic cathinone 3,4-methylenedioxypyrovalerone persistently increases impulsive choice in rats. Behav Pharmacol 2019; 30(7): 555-65.
[http://dx.doi.org/10.1097/FBP.0000000000000492] [PMID: 31211703]
[97]
Ray A, Chitre NM, Daphney CM, Blough BE, Canal CE, Murnane KS. Effects of the second-generation “bath salt” cathinone alpha-pyrrolidinopropiophenone (α-PPP) on behavior and monoamine neurochemistry in male mice. Psychopharmacology (Berl) 2019; 236(3): 1107-17.
[http://dx.doi.org/10.1007/s00213-018-5044-z] [PMID: 30276421]
[98]
Murnane KS, Perrine SA, Finton BJ, Galloway MP, Howell LL, Fantegrossi WE. Effects of exposure to amphetamine derivatives on passive avoidance performance and the central levels of monoamines and their metabolites in mice: Correlations between behavior and neurochemistry. Psychopharmacology (Berl) 2012; 220(3): 495-508.
[http://dx.doi.org/10.1007/s00213-011-2504-0] [PMID: 21993877]
[99]
Lengqvist J, Mata De Urquiza A, Bergman AC, et al. Polyunsaturated fatty acids including docosahexaenoic and arachidonic acid bind to the retinoid X receptor alpha ligand-binding domain. Mol Cell Proteomics 2004; 3(7): 692-703.
[http://dx.doi.org/10.1074/mcp.M400003-MCP200] [PMID: 15073272]
[100]
Lévesque D, Rouillard C. Nur77 and retinoid X receptors: Crucial factors in dopamine-related neuroadaptation. Trends Neurosci 2007; 30(1): 22-30.
[http://dx.doi.org/10.1016/j.tins.2006.11.006] [PMID: 17134767]
[101]
Taghizadeh M, Tamtaji OR, Dadgostar E, et al. The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson’s disease: A randomized, double-blind, placebo-controlled trial. Neurochem Int 2017; 108: 183-9.
[http://dx.doi.org/10.1016/j.neuint.2017.03.014] [PMID: 28342967]
[102]
Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: Dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol 2008; 8(5): 349-61.
[http://dx.doi.org/10.1038/nri2294] [PMID: 18437155]
[103]
Muldoon MF, Laderian B, Kuan DC, Sereika SM, Marsland AL, Manuck SB. Fish oil supplementation does not lower C-reactive protein or interleukin-6 levels in healthy adults. J Intern Med 2016; 279(1): 98-109.
[http://dx.doi.org/10.1111/joim.12442] [PMID: 26497831]
[104]
Flock MR, Skulas-Ray AC, Harris WS, Gaugler TL, Fleming JA, Kris-Etherton PM. Effects of supplemental long-chain omega-3 fatty acids and erythrocyte membrane fatty acid content on circulating inflammatory markers in a randomized controlled trial of healthy adults. Prostaglandins Leukot Essent Fatty Acids 2014; 91(4): 161-8.
[http://dx.doi.org/10.1016/j.plefa.2014.07.006] [PMID: 25091379]
[105]
Fayh APT, Borges K, Cunha GS, et al. Effects of n-3 fatty acids and exercise on oxidative stress parameters in type 2 diabetic: A randomized clinical trial. J Int Soc Sports Nutr 2018; 15: 18.
[http://dx.doi.org/10.1186/s12970-018-0222-2] [PMID: 29713249]
[106]
Sedighian M, Djafarian K, Dabiri S, Abdollahi M, Shab-Bidar S. Effect of omega-3 supplementation on expanded disability status scale and inflammatory cytokines in multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials. CNS Neurol Disord Drug Targets 2019; 18(7): 523-9.
[http://dx.doi.org/10.2174/1871527318666190516083008] [PMID: 31096898]
[107]
Dretsch MN, Johnston D, Bradley RS, MacRae H, Deuster PA, Harris WS. Effects of omega-3 fatty acid supplementation on neurocognitive functioning and mood in deployed U.S. soldiers: A pilot study. Mil Med 2014; 179(4): 396-403.
[http://dx.doi.org/10.7205/MILMED-D-13-00395] [PMID: 24690964]
[108]
Brinton EA, Mason RP. Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA). Lipids Health Dis 2017; 16(1): 23.
[http://dx.doi.org/10.1186/s12944-017-0415-8] [PMID: 28137294]
[109]
Hachem M, Géloën A, Van AL, et al. Efficient docosahexaenoic acid uptake by the brain from a structured phospholipid. Mol Neurobiol 2016; 53(5): 3205-15.
[http://dx.doi.org/10.1007/s12035-015-9228-9] [PMID: 26041661]
[110]
Shearer GC, Savinova OV, Harris WS. Fish oil -- how does it reduce plasma triglycerides? Biochim Biophys Acta 2012; 1821(5): 843-51.
[http://dx.doi.org/10.1016/j.bbalip.2011.10.011] [PMID: 22041134]
[111]
Hilleman D, Smer A. Prescription omega-3 fatty acid products and dietary supplements are not interchangeable. Manag Care 2016; 25(1): 46-52.
[PMID: 26882630]
[112]
Fialkow J. Omega-3 fatty acid formulations in cardiovascular disease: Dietary supplements are not substitutes for prescription products. Am J Cardiovasc Drugs 2016; 16(4): 229-39.
[113]
Davidson MH. Omega-3 fatty acids: New insights into the pharmacology and biology of docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid. Curr Opin Lipidol 2013; 24(6): 467-74.
[http://dx.doi.org/10.1097/MOL.0000000000000019] [PMID: 24184945]
[114]
Ballantyne CM, Bays HE, Philip S, et al. Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies. Atherosclerosis 2016; 253: 81-7.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.08.005] [PMID: 27596132]
[115]
Abdelhamid AS, Brown TJ, Brainard JS, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2018; 7CD003177.
[PMID: 30019766]
[116]
Lee MW, Park JK, Hong JW, et al. Beneficial effects of omega-3 fatty acids on low density lipoprotein particle size in patients with type 2 diabetes already under statin therapy. Diabetes Metab J 2013; 37(3): 207-11.
[http://dx.doi.org/10.4093/dmj.2013.37.3.207] [PMID: 23807924]
[117]
Freeman MP, McInerney K, Sosinsky AZ, Kwiatkowski MA, Cohen LS. Omega-3 fatty acids for atypical antipsychotic-associated hypertriglyceridemia. Ann Clin Psychiatry 2015; 27(3): 197-202.
[PMID: 26247219]
[118]
Chen Z, Venkat P, Seyfried D, Chopp M, Yan T, Chen J. Brain-heart interaction: Cardiac complications after stroke. Circ Res 2017; 121(4): 451-68.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311170] [PMID: 28775014]
[119]
Gopinath R, Ayya SS. Neurogenic stress cardiomyopathy: What do we need to know. Ann Card Anaesth 2018; 21(3): 228-34.
[http://dx.doi.org/10.4103/aca.ACA_176_17] [PMID: 30052207]
[120]
Finsterer J, Wahbi K. CNS-disease affecting the heart: Brain-heart disorders. J Neurol Sci 2014; 345(1-2): 8-14.
[http://dx.doi.org/10.1016/j.jns.2014.07.003] [PMID: 25034054]
[121]
Umegaki H. Neurodegeneration in diabetes mellitus. Adv Exp Med Biol 2012; 724: 258-65.
[http://dx.doi.org/10.1007/978-1-4614-0653-2_19] [PMID: 22411248]
[122]
Toth C. Diabetes and neurodegeneration in the brain. Handb Clin Neurol 2014; 126: 489-511.
[http://dx.doi.org/10.1016/B978-0-444-53480-4.00035-7] [PMID: 25410241]
[123]
Asih PR, Tegg ML, Sohrabi H, et al. Multiple mechanisms linking type 2 diabetes and Alzheimer’s disease: Testosterone as a modifier. J Alzheimers Dis 2017; 59(2): 445-66.
[http://dx.doi.org/10.3233/JAD-161259] [PMID: 28655134]
[124]
Bharadwaj P, Wijesekara N, Liyanapathirana M, et al. The link between type 2 diabetes and neurodegeneration: Roles for amyloid-β, amylin, and tau proteins. J Alzheimers Dis 2017; 59(2): 421-32.
[http://dx.doi.org/10.3233/JAD-161192] [PMID: 28269785]
[125]
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.
[http://dx.doi.org/10.3389/fnagi.2015.00052] [PMID: 25954194]
[126]
Siddiqui RA, Shaikh SR, Sech LA, Yount HR, Stillwell W, Zaloga GP. Omega 3-fatty acids: Health benefits and cellular mechanisms of action. Mini Rev Med Chem 2004; 4(8): 859-71.
[http://dx.doi.org/10.2174/1389557043403431] [PMID: 15544547]
[127]
Valentine RC, Valentine DL. Omega-3 fatty acids in cellular membranes: a unified concept. Prog Lipid Res 2004; 43(5): 383-402.
[http://dx.doi.org/10.1016/j.plipres.2004.05.004] [PMID: 15458813]
[128]
Cheshmehkani A, Senatorov IS, Dhuguru J, Ghoneim O, Moniri NH. Free-fatty acid receptor-4 (FFA4) modulates ROS generation and COX-2 expression via the C-terminal β-arrestin phosphosensor in raw 264.7 macrophages. Biochem Pharmacol 2017; 146: 139-50.
[http://dx.doi.org/10.1016/j.bcp.2017.09.008] [PMID: 28943238]
[129]
Prazeres DM, Martins SA. G protein-coupled receptors: An overview of signaling mechanisms and screening assays. Methods Mol Biol 2015; 1272: 3-19.
[http://dx.doi.org/10.1007/978-1-4939-2336-6_1] [PMID: 25563173]
[130]
Tikhonova IG. Application of gpcr structures for modelling of free fatty acid receptors. Handb Exp Pharmacol 2017; 236: 57-77.
[http://dx.doi.org/10.1007/164_2016_52] [PMID: 27757764]
[131]
Moniri NH. Free-fatty acid receptor-4 (GPR120): Cellular and molecular function and its role in metabolic disorders. Biochem Pharmacol 2016; 110-111: 1-15.
[http://dx.doi.org/10.1016/j.bcp.2016.01.021] [PMID: 26827942]
[132]
Alvarez-Curto E, Milligan G. Metabolism meets immunity: The role of free fatty acid receptors in the immune system. Biochem Pharmacol 2016; 114: 3-13.
[http://dx.doi.org/10.1016/j.bcp.2016.03.017] [PMID: 27002183]
[133]
Milligan G, Shimpukade B, Ulven T, Hudson BD. Complex pharmacology of free fatty acid receptors. Chem Rev 2017; 117(1): 67-110.
[http://dx.doi.org/10.1021/acs.chemrev.6b00056] [PMID: 27299848]
[134]
Kebede M, Ferdaoussi M, Mancini A, et al. Glucose activates free fatty acid receptor 1 gene transcription via phosphatidylinositol-3-kinase-dependent O-GlcNAcylation of pancreas-duodenum homeobox-1. Proc Natl Acad Sci USA 2012; 109(7): 2376-81.
[http://dx.doi.org/10.1073/pnas.1114350109] [PMID: 22308370]
[135]
Lu J, Byrne N, Wang J, et al. Structural basis for the cooperative allosteric activation of the free fatty acid receptor GPR40. Nat Struct Mol Biol 2017; 24(7): 570-7.
[http://dx.doi.org/10.1038/nsmb.3417] [PMID: 28581512]
[136]
Nakamoto K. A new pain regulatory system via the brain long chain fatty acid receptor GPR40/FFA1 signal. Yakugaku Zasshi 2017; 137(2): 199-204.
[http://dx.doi.org/10.1248/yakushi.16-00208] [PMID: 28154332]
[137]
Burns RN, Moniri NH. Agonism with the omega-3 fatty acids alpha-linolenic acid and docosahexaenoic acid mediates phosphorylation of both the short and long isoforms of the human GPR120 receptor. Biochem Biophys Res Commun 2010; 396(4): 1030-5.
[http://dx.doi.org/10.1016/j.bbrc.2010.05.057] [PMID: 20471368]
[138]
Larrieu T, Layé S. Food for mood: Relevance of nutritional omega-3 fatty acids for depression and anxiety. Front Physiol 2018; 9: 1047.
[http://dx.doi.org/10.3389/fphys.2018.01047] [PMID: 30127751]
[139]
Ichimura A, Hirasawa A, Hara T, Tsujimoto G. Free fatty acid receptors act as nutrient sensors to regulate energy homeostasis. Prostaglandins Other Lipid Mediat 2009; 89(3-4): 82-8.
[http://dx.doi.org/10.1016/j.prostaglandins.2009.05.003] [PMID: 19460454]
[140]
Cheshmehkani A, Senatorov IS, Kandi P, et al. Fish oil and flax seed oil supplemented diets increase FFAR4 expression in the rat colon. Inflamm Res 2015; 64(10): 809-15.
[http://dx.doi.org/10.1007/s00011-015-0864-3] [PMID: 26275932]
[141]
Oh DY, Talukdar S, Bae EJ, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010; 142(5): 687-98.
[http://dx.doi.org/10.1016/j.cell.2010.07.041] [PMID: 20813258]
[142]
Muredda L, Kępczyńska MA, Zaibi MS, Alomar SY, Trayhurn P. IL-1β and TNFα inhibit GPR120 (FFAR4) and stimulate GPR84 (EX33) and GPR41 (FFAR3) fatty acid receptor expression in human adipocytes: Implications for the anti-inflammatory action of n-3 fatty acids. Arch Physiol Biochem 2018; 124(2): 97-108.
[http://dx.doi.org/10.1080/13813455.2017.1364774] [PMID: 28835131]
[143]
Song T, Yang Y, Zhou Y, Wei H, Peng J. GPR120: A critical role in adipogenesis, inflammation, and energy metabolism in adipose tissue. Cell Mol Life Sci 2017; 74(15): 2723-33.
[http://dx.doi.org/10.1007/s00018-017-2492-2] [PMID: 28285320]
[144]
Alkahtani R, Mahavadi S, Alqudah M, Murthy K, Grider J. Activation of long-chain free fatty acid receptor FFAR1 (GPR40) and FFAR4 (GPR120) causes release of brain-derived neurotropic factor from enteric glial cells (905.2). FASEB J 2014; 28(1_supplement): 905-2.
[145]
Bekinschtein P, Cammarota M, Medina JH. BDNF and memory processing. Neuropharmacology 2014; 76(Pt C): 677-83.
[http://dx.doi.org/10.1016/j.neuropharm.2013.04.024] [PMID: 23688925]
[146]
Björkholm C, Monteggia LM. BDNF - a key transducer of antidepressant effects. Neuropharmacology 2016; 102: 72-9.
[http://dx.doi.org/10.1016/j.neuropharm.2015.10.034] [PMID: 26519901]
[147]
Kojima M, Mizui T. BDNF Propeptide: A novel modulator of synaptic plasticity. Vitam Horm 2017; 104: 19-28.
[http://dx.doi.org/10.1016/bs.vh.2016.11.006] [PMID: 28215295]
[148]
Kumar YP, Srinivas GS. E YM, Malla L, Rao AA. Agonistic approach of omega-3, omega-6 and its metabolites with BDNF: An in-silico study. Bioinformation 2013; 9(18): 908-11.
[http://dx.doi.org/10.6026/97320630009908] [PMID: 24307768]
[149]
Milligan G, Alvarez-Curto E, Watterson KR, Ulven T, Hudson BD. Characterizing pharmacological ligands to study the long-chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4. Br J Pharmacol 2015; 172(13): 3254-65.
[http://dx.doi.org/10.1111/bph.12879] [PMID: 25131623]
[150]
Tikhonova IG, Poerio E. Free fatty acid receptors: Structural models and elucidation of ligand binding interactions. BMC Struct Biol 2015; 15: 16.
[http://dx.doi.org/10.1186/s12900-015-0044-2] [PMID: 26346819]
[151]
Lückmann M, Trauelsen M, Bentsen MA, et al. Molecular dynamics-guided discovery of an ago-allosteric modulator for GPR40/FFAR1. Proc Natl Acad Sci USA 2019; 116(14): 7123-8.
[http://dx.doi.org/10.1073/pnas.1811066116]
[152]
Tikhonova IG, Sum CS, Neumann S, et al. Discovery of novel agonists and antagonists of the free fatty acid receptor 1 (FFAR1) using virtual screening. J Med Chem 2008; 51(3): 625-33.
[http://dx.doi.org/10.1021/jm7012425] [PMID: 18193825]
[153]
Hudson BD, Shimpukade B, Milligan G, Ulven T. The molecular basis of ligand interaction at free fatty acid receptor 4 (FFA4/GPR120). J Biol Chem 2014; 289(29): 20345-58.
[http://dx.doi.org/10.1074/jbc.M114.561449] [PMID: 24860101]
[154]
Watterson KR, Hudson BD, Ulven T, Milligan G. Treatment of type 2 diabetes by free fatty acid receptor agonists. Front Endocrinol (Lausanne) 2014; 5: 137.
[http://dx.doi.org/10.3389/fendo.2014.00137] [PMID: 25221541]
[155]
Ichimura A, Hasegawa S, Kasubuchi M, Kimura I. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol 2014; 5: 236.
[http://dx.doi.org/10.3389/fphar.2014.00236] [PMID: 25414667]
[156]
Suckow AT, Briscoe CP. Key questions for translation of FFA receptors: From pharmacology to medicines. Handb Exp Pharmacol 2017; 236: 101-31.
[http://dx.doi.org/10.1007/164_2016_45] [PMID: 27873087]
[157]
Christiansen E, Hansen SV, Urban C, et al. Discovery of TUG-770: A highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes. ACS Med Chem Lett 2013; 4(5): 441-5.
[http://dx.doi.org/10.1021/ml4000673] [PMID: 23687558]
[158]
Tsuda N, Kawaji A, Sato T, et al. A novel free fatty acid receptor 1 (GPR40/FFAR1) agonist, MR1704, enhances glucose-dependent insulin secretion and improves glucose homeostasis in rats. Pharmacol Res Perspect 2017; 5(4)
[http://dx.doi.org/10.1002/prp2.340] [PMID: 28805970]
[159]
Luo J, Swaminath G, Brown SP, et al. A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents. PLoS One 2012; 7(10): e46300.
[http://dx.doi.org/10.1371/journal.pone.0046300] [PMID: 23056280]
[160]
Christiansen E, Urban C, Merten N, et al. Discovery of potent and selective agonists for the free fatty acid receptor 1 (FFA(1)/GPR40), a potential target for the treatment of type II diabetes. J Med Chem 2008; 51(22): 7061-4.
[http://dx.doi.org/10.1021/jm8010178] [PMID: 18947221]
[161]
Li Z, Qiu Q, Xu X, et al. Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes. Eur J Med Chem 2016; 113: 246-57.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.040] [PMID: 26945112]
[162]
Lin DC, Guo Q, Luo J, et al. Identification and pharmacological characterization of multiple allosteric binding sites on the free fatty acid 1 receptor. Mol Pharmacol 2012; 82(5): 843-59.
[http://dx.doi.org/10.1124/mol.112.079640] [PMID: 22859723]
[163]
Briscoe CP, Peat AJ, McKeown SC, et al. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: Identification of agonist and antagonist small molecules. Br J Pharmacol 2006; 148(5): 619-28.
[http://dx.doi.org/10.1038/sj.bjp.0706770] [PMID: 16702987]
[164]
Martin C, Passilly-Degrace P, Chevrot M, et al. Lipid-mediated release of GLP-1 by mouse taste buds from circumvallate papillae: Putative involvement of GPR120 and impact on taste sensitivity. J Lipid Res 2012; 53(11): 2256-65.
[http://dx.doi.org/10.1194/jlr.M025874] [PMID: 22904345]
[165]
Sun Q, Hirasawa A, Hara T, et al. Structure-activity relationships of GPR120 agonists based on a docking simulation. Mol Pharmacol 2010; 78(5): 804-10.
[http://dx.doi.org/10.1124/mol.110.066324] [PMID: 20685848]
[166]
Hudson BD, Shimpukade B, Mackenzie AE, et al. The pharmacology of TUG-891, a potent and selective agonist of the Free Fatty Acid receptor 4 (FFA4/GPR120), demonstrates both potential opportunity and possible challenges to therapeutic agonism. Mol Pharmacol 2013; 84(5): 710-25.
[http://dx.doi.org/10.1124/mol.113.087783] [PMID: 23979972]
[167]
Thathiah A, Horré K, Snellinx A, et al. β-arrestin 2 regulates Aβ generation and γ-secretase activity in Alzheimer’s disease. Nat Med 2013; 19(1): 43-9.
[http://dx.doi.org/10.1038/nm.3023] [PMID: 23202293]
[168]
Ludtmann MHR, Abramov AY. Mitochondrial calcium imbalance in Parkinson’s disease. Neurosci Lett 2018; 663: 86-90.
[http://dx.doi.org/10.1016/j.neulet.2017.08.044] [PMID: 28838811]
[169]
Hara T, Hirasawa A, Sun Q, et al. Novel selective ligands for free fatty acid receptors GPR120 and GPR40. Naunyn Schmiedebergs Arch Pharmacol 2009; 380(3): 247-55.
[http://dx.doi.org/10.1007/s00210-009-0425-9] [PMID: 19471906]
[170]
Shimpukade B, Hudson BD, Hovgaard CK, Milligan G, Ulven T. Discovery of a potent and selective GPR120 agonist. J Med Chem 2012; 55(9): 4511-5.
[http://dx.doi.org/10.1021/jm300215x] [PMID: 22519963]
[171]
Hauge M, Vestmar MA, Husted AS, et al. GPR40 (FFAR1) - Combined Gs and Gq signaling in vitro is associated with robust incretin secretagogue action ex vivo and in vivo. Mol Metab 2014; 4(1): 3-14.
[http://dx.doi.org/10.1016/j.molmet.2014.10.002] [PMID: 25685685]
[172]
Stubbs CD, Smith AD. The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 1984; 779(1): 89-137.
[http://dx.doi.org/10.1016/0304-4157(84)90005-4] [PMID: 6229284]
[173]
Otieno MA, Snoeys J, Lam W, et al. Fasiglifam (TAK-875): Mechanistic investigation and retrospective identification of hazards for drug induced liver injury. Toxicol Sci 2018; 163(2): 374-84.
[174]
Bradberry JC, Hilleman DE. Overview of omega-3 fatty acid therapies. P&T 2013; 38(11): 681-91.
[175]
Schuchardt JP, Hahn A. Bioavailability of long-chain omega-3 fatty acids. Prostaglandins Leukot Essent Fatty Acids 2013; 89(1): 1-8.
[http://dx.doi.org/10.1016/j.plefa.2013.03.010] [PMID: 23676322]
[176]
Miura K, Hughes MCB, Ungerer JPJ, Smith DD, Green AC. Absolute versus relative measures of plasma fatty acids and health outcomes: Example of phospholipid omega-3 and omega-6 fatty acids and all-cause mortality in women. Eur J Nutr 2018; 57(2): 713-22.
[http://dx.doi.org/10.1007/s00394-016-1358-y] [PMID: 27995316]
[177]
Köhler A, Sarkkinen E, Tapola N, Niskanen T, Bruheim I. Bioavailability of fatty acids from krill oil, krill meal and fish oil in healthy subjects--a randomized, single-dose, cross-over trial. Lipids Health Dis 2015; 14(1): 19.
[http://dx.doi.org/10.1186/s12944-015-0015-4] [PMID: 25884846]
[178]
Ottestad I, Nordvi B, Vogt G, et al. Bioavailability of n-3 fatty acids from n-3-enriched foods and fish oil with different oxidative quality in healthy human subjects: A randomised single-meal cross-over study. J Nutr Sci 2016; 5: e43.
[http://dx.doi.org/10.1017/jns.2016.34] [PMID: 28620470]
[179]
Cholewski M, Tomczykowa M, Tomczyk M. A comprehensive review of chemistry, sources and bioavailability of omega-3 fatty acids. Nutrients 2018; 10(11): E1662.
[http://dx.doi.org/10.3390/nu10111662] [PMID: 30400360]
[180]
Cicero AF, Morbini M, Borghi C. Do we need ‘new’ omega-3 polyunsaturated fatty acids formulations? Expert Opin Pharmacother 2015; 16(3): 285-8.
[http://dx.doi.org/10.1517/14656566.2015.991308] [PMID: 25474717]
[181]
Ghasemifard S, Sinclair AJ, Kaur G, Lewandowski P, Turchini GM. What is the most effective way of increasing the bioavailability of dietary long chain omega-3 fatty acids-daily vs. weekly administration of fish oil? Nutrients 2015; 7(7): 5628-45.
[http://dx.doi.org/10.3390/nu7075241] [PMID: 26184297]
[182]
Ghasemifard S, Turchini GM, Sinclair AJ. Omega-3 long chain fatty acid “bioavailability”: A review of evidence and methodological considerations. Prog Lipid Res 2014; 56: 92-108.
[http://dx.doi.org/10.1016/j.plipres.2014.09.001] [PMID: 25218856]
[183]
Davidson MH, Johnson J, Rooney MW, Kyle ML, Kling DF. A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: The ECLIPSE (Epanova(®) compared to Lovaza(®) in a pharmacokinetic single-dose evaluation) study. J Clin Lipidol 2012; 6(6): 573-84.
[http://dx.doi.org/10.1016/j.jacl.2012.01.002] [PMID: 23312053]
[184]
Maki KC, Dicklin MR. Strategies to improve bioavailability of omega-3 fatty acids from ethyl ester concentrates. Curr Opin Clin Nutr Metab Care 2019; 22(2): 116-23.
[http://dx.doi.org/10.1097/MCO.0000000000000537] [PMID: 30550388]
[185]
Lopez-Toledano MA, Thorsteinsson T, Daak A, et al. A novel ω-3 acid ethyl ester formulation incorporating advanced lipid technologiesTM (ALT®) improves docosahexaenoic acid and eicosapentaenoic acid bioavailability compared with Lovaza®. Clin Ther 2017; 39(3): 581-91.
[http://dx.doi.org/10.1016/j.clinthera.2017.01.020] [PMID: 28189364]
[186]
Walker R, Decker EA, McClements DJ. Development of food-grade nanoemulsions and emulsions for delivery of omega-3 fatty acids: Opportunities and obstacles in the food industry. Food Funct 2015; 6(1): 42-55.
[http://dx.doi.org/10.1039/C4FO00723A] [PMID: 25384961]
[187]
Hinriksdottir HH, Jonsdottir VL, Sveinsdottir K, Martinsdottir E, Ramel A. Bioavailability of long-chain n-3 fatty acids from enriched meals and from microencapsulated powder. Eur J Clin Nutr 2015; 69(3): 344-8.
[http://dx.doi.org/10.1038/ejcn.2014.250] [PMID: 25406967]
[188]
Walters WP. Going further than Lipinski’s rule in drug design. Expert Opin Drug Discov 2012; 7(2): 99-107.
[http://dx.doi.org/10.1517/17460441.2012.648612] [PMID: 22468912]
[189]
Freund Levi Y, Vedin I, Cederholm T, et al. Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer’s disease: The OmegAD study. J Intern Med 2014; 275(4): 428-36.
[http://dx.doi.org/10.1111/joim.12166] [PMID: 24410954]
[190]
Gillies PJ, Harris WS, Kris-Etherton PM. Omega-3 fatty acids in food and pharma: The enabling role of biotechnology. Curr Atheroscler Rep 2011; 13(6): 467-73.
[http://dx.doi.org/10.1007/s11883-011-0206-z] [PMID: 21892757]


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VOLUME: 18
ISSUE: 10
Year: 2019
Page: [735 - 749]
Pages: 15
DOI: 10.2174/1871527318666191114093749
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