Parkinson Hastalığı Patogenezinde Esansiyel Yağ Asitleri ve Kolesterolün Etkileri

Yıl 2020, Cilt: 11 Sayı: 1, 120 - 126, 03.03.2020

Meltem Mermer , Hilal Yıldıran

Öz

Parkinson
hastalığı (PH) bilişsel ve motor semptomları içeren nörodejeneratif bir
hastalıktır. Beyinin vücuttaki en yağlı ve yüksek oranda kolesterol içeren bir
organ olması nedeniyle normal fonksiyonlarını sürdürülmek için yağlara ve
kolesterole ihtiyaç duyar. Elzem yağ asitleri beynin birçok hücresel
fonksiyonunda rol almaktadır. Linoleik asit ve α-linolenik asit vücut
tarafından sentezlenemediği için elzem yağ asitleri olup diyet ile alınmalıdır.
Bu iki esansiyel yağ asidi daha uzun zincirli çoklu doymamış yağ asitlerinin (PUFA)
sentezi için öncüdürler. Beyin serbest PUFA seviyeleri oksidatif stres ve
inflamasyon bağlı olarak artmaktadır. Ayrıca oksidatif stres beyinde yüksek
seviyelerde bulunan DHA ve AA’in peroksidasyonuna ve bunun sonucunda da dopaminerjik
sistem nörodejenerasyonuna neden olmaktadır. Diyetin esansiyel yağ asidi
içeriği nörotransmitter sistemleri etkilemektedir. Kronik omega-3 (w-3) yağ
asidi eksikliği dopamin reseptörü bağlanmasında azalmaya, serotonin reseptörü
yoğunluğunda artışa ve dopamin metabolizmasında değişikliklere neden
olabilirken substantia nigrada görülen 
dopaminerjik nöron kaybının az da olsa DHA tarafından önlendiği deneysel
olarak gösterilmiştir. Beyin fonksiyonlarının devamlılığı için önemli olan kolesterolün
de kanda normal seviyelerin üstüne çıkması beyinde oksidatif stresi ve buna
bağlı olarak PH riskini arttırabilir. Diyet esansiyel yağ asitleri ve
kolesterol seviyesi ile PH gelişimi riski arasındaki ilişkiyi inceleyen
çalışmaların birbirleri ile çelişen sonuçları bulunmaktadır. Bu nedenle
esansiyel yağ asitleri ve kolesterolün PH’nın oluşumu, önlemesi ve/veya
semptomları azaltma etkisi konularını kesinleştirecek daha geniş çaplı
araştırmalara ihtiyaç vardır.

Anahtar Kelimeler

Parkinson hastalığı, esansiyel yağ asitleri

Kaynakça

• 1. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. J Neuron 2003; 39(6): 889-909.
• 2. De Lau LM, Breteler MM. Epidemiology of parkinson's disease. J The Lancet Neurology 2006; 5(6): 525-35.
• 3. Dorsey E, Constantinescu R, Thompson J, Biglan K, Holloway R, Kieburtz K, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. J Neurol 2007; 68(5): 384-6.
• 4. Durmus H, Gokalp MA, Hanagasi HA. Prevalence of Parkinson’s disease in Baskale, Turkey: a population based study. Neurol Sci 2015; 36(3): 411-3.
• 5. Türk Nöroloji Derneği [internet]. [07.09.2019]. https://www.noroloji.org.tr.
• 6. Yehuda S, Rabinovitz S, Mostofsky D. Essential fatty acids and the brain: from infancy to aging. Neurobiol Aging 2005; 26(1): 98-102.
• 7. Youdim KA, Martin A, Joseph JA. Essential fatty acids and the brain: possible health implications. Int J Dev Neurosci 2000; 18(4-5): 383-99.
• 8. Chang C-Y, Ke D-S, Chen J-Y. Essential fatty acids and human brain. J Acta Neurol Taiwan 2009; 18(4): 231-41.
• 9. Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell 2015; 6(4): 254-64.
• 10. Bourre J. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during ageing. J of Nutrition Health Aging 2004; 8(3): 163-75.
• 11. Carrié I, Clément M, de Javel D, Francès H, Bourre J-M. Specific phospholipid fatty acid composition of brain regions in mice: effects of n–3 polyunsaturated fatty acid deficiency and phospholipid supplementation. J Lipid Res 2000; 41(3): 465-72.
• 12. Delion S, Chalon S, Hérault J, Guilloteau D, Besnard J-C, Durand G. Chronic dietary α-linolenic acid deficiency alters dopaminergic and serotoninergic neurotransmission in rats. J Nutr 1994; 124(12): 2466-76.
• 13. Favreliere S, Barrier L, Durand G, Chalon S, Tallineau C. Chronic dietary n‐3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum. Lipids 1998; 33(4): 401-7.
• 14. Arterburn LM, Hall EB, Oken H. Distribution, interconversion, and dose response of n− 3 fatty acids in humans. Am J Clin Nutr 2006; 83(6): 1467-76.
• 15. Sharon R, Bar-Joseph I, Mirick GE, Serhan CN, Selkoe DJ. Altered fatty acid composition of dopaminergic neurons expressing α-synuclein and human brains with α-synucleinopathies. J Biol Chem 2003; 278(50): 49874-81.
• 16. Ruipérez V, Darios F, Davletov B. Alpha-synuclein, lipids and Parkinson’s disease. Prog Lipid Res 2010; 49(4): 420-8.
• 17. Haag M. Essential fatty acids and the brain. Can J Psychiatry 2003; 48(3): 195-203.
• 18. Whelan J. (n-6) and (n-3) Polyunsaturated fatty acids and the aging brain: food for thought. J Nutr 2008; 138(12): 2521-2.
• 19. Calon F, Cicchetti F. Can we prevent Parkinson’s disease with n-3 polyunsaturated fatty acids? Future Lipidol 2008; 3(2): 133-7.
• 20. Elbaz A, Carcaillon L, Kab S, Moisan F. Epidemiology of Parkinson's disease. Rev Neurol 2016; 172(1): 14-26.
• 21. Horstink MW, Van Engelen BG. The effect of coenzyme Q10 therapy in Parkinson disease could be symptomatic. Arch Neurol 2003; 60(8): 1170-2.
• 22. Ozsoy O, Seval-Celik Y, Hacioglu G, Yargicoglu P, Demir R, Agar A, et al. The influence and the mechanism of docosahexaenoic acid on a mouse model of Parkinson’s disease. Neurochem Int 2011; 59(5): 664-70.
• 23. Beyer K. Mechanistic aspects of Parkinson’s disease: α-synuclein and the biomembrane. Cell Biochem Biophys 2007; 47(2): 285-99.
• 24. Galvagnion C, Brown JW, Ouberai MM, Flagmeier P, Vendruscolo M, Buell AK, et al. Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein. Proceedings of the National Academy of Sciences 2016; 113(26): 7065-70.
• 25. Maes M, Galecki P, Chang YS, Berk M. A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro) degenerative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35(3): 676-92.
• 26. Calder PC. Omega-3 fatty acids and inflammatory processes. Nutrients 2010; 2(3): 355-74.
• 27. Lu Y, Zhao L-X, Cao D-L, Gao Y-J. Spinal injection of docosahexaenoic acid attenuates carrageenan-induced inflammatory pain through inhibition of microglia-mediated neuroinflammation in the spinal cord. Neuroscience 2013; 241: 22-31.
• 28. Whitton P. Inflammation as a causative factor in the aetiology of Parkinson's disease. Br J Pharmacol 2007; 150(8): 963-76.
• 29. Ji A, Diao H, Wang X, Yang R, Zhang J, Luo W, et al. n-3 polyunsaturated fatty acids inhibit lipopolysaccharide-induced microglial activation and dopaminergic injury in rats. Neurotoxicology 2012; 33(4): 780-8.
• 30. Samadi P, Grégoire L, Rouillard C, Bédard PJ, Di Paolo T, Lévesque D. Docosahexaenoic acid reduces levodopa‐induced dyskinesias in 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine monkeys. Ann Neurol 2006; 59(2): 282-8.
• 31. Agim ZS, Cannon JR. Dietary factors in the etiology of Parkinson’s disease. J BioMed Research International 2015; 2015.
• 32. Wainwright PE. Dietary essential fatty acids and brain function: a developmental perspective on mechanisms. Proceedings of the Nutrition Society 2002; 61(1): 61-9.
• 33. Delion S, Chalon S, Guilloteau D, Besnard JC, Durand G. α‐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.
• 34. Zimmer L, Delpal S, Guilloteau D, Aıoun J, Durand G, Chalon S. Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex. J Neuroscience letters. Neurosci Lett 2000; 284(1-2): 25-8.
• 35. Morris JK, Bomhoff GL, Stanford JA, Geiger PC. Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet. Am J Physiol Regul Integr Comp Physiol 2010; 299(4): 1082-90.
• 36. Perrin RJ, Woods WS, Clayton DF, George JM. Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J Biol Chem 2001; 276(45): 41958-62.
• 37. 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(51): 15610-6.
• 38. Aarsland D, Brønnick K, Ehrt U, De Deyn PP, Tekin S, Emre M, et al. Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress. Neurol Neurosurg Psychiatry 2007; 78(1): 36-42.
• 39. Ravina B, Camicioli R, Como P, Marsh L, Jankovic J, Weintraub D, et al. The impact of depressive symptoms in early Parkinson disease. Neurology 2007; 69(4): 342-7.
• 40. Pomponi M, Loria G, Salvati S, Di Biase A, Conte G, Villella C, et al. DHA effects in Parkinson disease depression. Basal Ganglia 2014; 4(2): 61-6.
• 41. da Silva TM, Munhoz RP, Alvarez C, Naliwaiko K, Kiss Á, Andreatini R, et al. Depression in Parkinson's disease: a double-blind, randomized, placebo-controlled pilot study of omega-3 fatty-acid supplementation. Journal of Affective Disorders 2008; 111(2-3): 351-9.
• 42. 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. Movement Disorders 1999; 14(1): 21-7.
• 43. Hellenbrand W, Seidler A, Boeing H, Robra B-P, Vieregge P, Nischan P, et al. Diet and Parkinson's disease I. Neurology 1996; 47(3): 636-43.
• 44. Logroscino G, Marder K, Graziano J, Freyer G, Slavkovich V, Lojacono N, et al. Dietary iron, animal fats, and risk of Parkinson's disease. Mov Disord 1998; 13: 13-6.
• 45. Scheider W, Hershey L, Vena J, Holmlund T, Marshall J, Freudenheim J. Dietary antioxidants and other dietary factors in the etiology of Parkinson's disease. Mov Disord 1997; 12(2): 190-6.
• 46. Vieregge P, Maravic C, Friedrich H-J. Life-style and dietary factors early and late in Parkinson’s disease. Can J Neurol Sci 1992; 19(2): 170-3.
• 47. Chen H, Zhang SM, Hernán MA, Willett WC, Ascherio A. Dietary intakes of fat and risk of Parkinson’s disease. Am J Epidemiol 2003; 157(11): 1007-14.
• 48. Dong J, Beard JD, Umbach DM, Park Y, Huang X, Blair A, et al. Dietary fat intake and risk for Parkinson's disease. Mov Disord 2014; 29(13): 1623-30.
• 49. Kamel F, Goldman SM, Umbach DM, Chen H, Richardson G, Barber MR, et al. Dietary fat intake, pesticide use, and Parkinson's disease. Parkinsonism Related Disorders 2014; 20(1): 82-7.
• 50. Miyake Y, Sasaki S, Tanaka K, Fukushima W, Kiyohara C, Tsuboi Y, et al. Dietary fat intake and risk of Parkinson's disease: a case-control study in Japan. J Neurol Sci 2010; 288(1-2): 117-22.
• 51. Tan LC, Methawasin K, Tan E-K, Tan JH, Au W-L, Yuan J-M, et al. Dietary cholesterol, fats and risk of Parkinson's disease in the Singapore Chinese Health Study. J Neurol Neurosurg Psychiatry 2016; 87(1): 86-92.
• 52. De Lau L, Bornebroek M, Witteman J, Hofman A, Koudstaal PJ, Breteler M. Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. J Neurol 2005; 64(12): 2040-5.
• 53. Ahmad SO, Park J-H, 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. J Neuroscience Letters 2008; 438(3): 303-7.
• 54. Cardoso HD, dos Santos Junior EF, de Santana DF, Gonçalves-Pimentel C, Angelim MK, Isaac AR, et al. Omega-3 deficiency and neurodegeneration in the substantia nigra: involvement of increased nitric oxide production and reduced BDNF expression. J Biochimica et Biophysica Acta 2014; 1840(6): 1902-12.
• 55. Passos PP, Borba JMC, Rocha-de-Melo AP, Guedes RCA, da Silva RP, Melo Filho WT, et al. Dopaminergic cell populations of the rat substantia nigra are differentially affected by essential fatty acid dietary restriction over two generations. J Chem Neuroanat 2012; 44(2): 66-75.
• 56. Ghribi O, Larsen B, Schrag M, Herman MM. High cholesterol content in neurons increases BACE, β-amyloid, and phosphorylated tau levels in rabbit hippocampus. Exp Neurol 2006; 200(2): 460-7.
• 57. Paul R, Choudhury A, Borah A. Cholesterol–a putative endogenous contributor towards Parkinson's disease. Neurochem Int 2015; 90: 125-33.
• 58. Bar‐On P, Crews L, Koob AO, Mizuno H, Adame A, Spencer B, et al. Statins reduce neuronal α‐synuclein aggregation in in vitro models of Parkinson’s disease. J Neurochem 2008; 105(5): 1656-67.
• 59. Fantini J, Carlus D, Yahi N. The fusogenic tilted peptide (67–78) of α-synuclein is a cholesterol binding domain. Biochim Biophys Acta-Biomembranes 2011; 1808(10): 2343-51.
• 60. De Lau LM, Koudstaal PJ, Hofman A, Breteler MM. Serum cholesterol levels and the risk of Parkinson's disease. Am J Epidemiol 2006; 164(10): 998-1002.
• 61. Huang X, Alonso A, Guo X, Umbach DM, Lichtenstein ML, Ballantyne CM, et al. Statins, plasma cholesterol, and risk of Parkinson's disease: a prospective study. Mov Disord 2015; 30(4): 552-9.
• 62. Huang X, Auinger P, Eberly S, Oakes D, Schwarzschild M, Ascherio A, et al. Serum cholesterol and the progression of Parkinson's disease: results from DATATOP. PLoS One 2011; 6(8): e22854.
• 63. Hu G, Antikainen R, Jousilahti P, Kivipelto M, Tuomilehto J. Total cholesterol and the risk of Parkinson disease. Neurology 2008; 70(21): 1972-9.
• 64. Huang X, Abbott RD, Petrovitch H, Mailman RB, Ross GW. Low LDL cholesterol and increased risk of Parkinson's disease: prospective results from Honolulu‐Asia Aging Study. Mov Disord 2008; 23(7): 1013-8.
• 65. Huang X, Chen H, Miller WC, Mailman RB, Woodard JL, Chen PC, et al. Lower low‐density lipoprotein cholesterol levels are associated with Parkinson's disease. Mov Disord 2007; 22(3): 377-81.
• 66. Bosco DA, Fowler DM, Zhang Q, Nieva J, Powers ET, Wentworth Jr P, et al. Elevated levels of oxidized cholesterol metabolites in Lewy body disease brains accelerate α-synuclein fibrilization. Nature Chemical Biology 2006; 2(5): 249.
• 67. Marwarha G, Rhen T, Schommer T, Ghribi O. The oxysterol 27‐hydroxycholesterol regulates α‐synuclein and tyrosine hydroxylase expression levels in human neuroblastoma cells through modulation of liver X receptors and estrogen receptors–relevance to Parkinson’s disease. J Neurochem 2011; 119(5): 1119-36.