The Effect of DNA Methylation and Some Nutritional Factors in Parkinson's Disease

Yıl 2024, Cilt: 4 Sayı: 3, 353 - 366, 30.09.2024

Aslıhan Atar

https://doi.org/10.52369/togusagbilderg.1389480

Öz

In this article, the epigenetic effects in Parkinson's disease and particularly the relationship between DNA methylation, nutrition-related factors, and the disease are discussed. Parkinson's disease is a neurodegenerative disorder that is known to be associated with genetic predisposition, with various genes shown to be implicated in its development. In recent years, the significance of epigenetic mechanisms in Parkinson's disease has been emphasized. Specifically, epigenetic changes such as DNA methylation have been demonstrated to play a role in the development of Parkinson's disease. Hypermethylation or hypomethylation of genes related to Parkinson's disease has been found, and these alterations have been shown to be influential in the progression of the disease. The importance of nutrition-related factors in Parkinson's disease is also considered. Folate deficiency, leading to increased homocysteine levels, may contribute to neurotoxicity and dopaminergic cell death, thereby promoting disease progression. Certain gene interactions through coffee and caffeine have also been associated with Parkinson's disease; however, inconsistent results have been observed due to interindividual variations in caffeine metabolism. Prolonged exposure to the heavy metal manganese is linked to Parkinson's disease as it can affect dopaminergic, glutamatergic, and GABAergic neurotransmission, induce oxidative stress, and trigger neuroinflammation. Nevertheless, further research is needed to fully understand the connection between Parkinson's disease and epigenetic mechanisms. Understanding the underlying epigenetic modifications in Parkinson's disease will aid in developing preventive strategies and provide new avenues for its treatment.

Anahtar Kelimeler

DNA methylation, Epigenetic, Nutrition, Parkinson’s disease

Parkinson Hastalığında DNA Metilasyonunun ve Beslenmeye Bağlı Bazı Faktörlerin Etkisi

Öz

Bu makalede, Parkinson hastalığındaki epigenetik etkiler ve özellikle DNA metilasyonu ve beslenmeye bağlı bazı faktörlerin hastalık ile ilişkisi ele alınmıştır. Parkinson hastalığı, genetik yatkınlıkla ilişkilendirilen ve çeşitli genlerin hastalığın gelişimiyle ilişkili olduğu gösterilen bir nörodejeneratif bozukluktur. Son yıllarda, Parkinson hastalığındaki epigenetik mekanizmaların önemi vurgulanmıştır. Özellikle, DNA metilasyonu gibi epigenetik değişikliklerin Parkinson hastalığının gelişiminde etkili olduğu gösterilmiştir. Parkinson hastalığıyla ilişkili genlerin DNA metilasyonunda hipo veya hipermetillenme bulunmuş ve bu durum hastalığın ilerlemesinde etkili olmuştur. Ayrıca, Parkinson hastalığında beslenme faktörlerinin önemi de dikkate alınmaktadır. Folat eksikliği, artmış homosistein seviyelerine ve dolayısıyla nörotoksisiteye ve dopaminerjik hücre ölümüne katkıda bulunarak hastalığın ilerlemesine katkı sağlayabilir. Kahve ve kafein aracılığıyla bazı gen etkileşimleri de Parkinson hastalığıyla ilişkilendirilebilir, ancak kafein metabolizması bireyler arasında farklılık gösterdiği için çalışmalar tutarsız sonuçlar vermektedir. Ağır metal olan manganezin uzun süreli maruziyeti, Parkinson hastalığıyla ilişkilendirilen dopaminerjik, glutamaterjik ve GABA iletimini etkileyebilir, oksidatif stresi ve nöroinflamasyonu tetikleyebilir. Bununla birlikte, Parkinson hastalığı ile epigenetik mekanizmalar arasındaki ilişkinin tam olarak anlaşılabilmesi için daha fazla araştırmaya ihtiyaç vardır. Parkinson hastalığının altında yatan epigenetik modifikasyonları anlamak hastalığa karşı önleyici çözümler bulunmasına ve tedavisi için yeni alternatifler sağlamaya yardımcı olacaktır.

Anahtar Kelimeler

Beslenme, DNA metilasyonu, Epigenetik, Parkinson hastalığı

Kaynakça

• 1. Kalia L V., Lang AE. Parkinson’s disease. The Lancet. 2015; 386(9996):896–912.
• 2. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol. 2016; 15(12):1257–72.
• 3. Brown TP, Rumsby PC, Capleton AC, Rushton L, Levy LS. Pesticides and Parkinson’s disease--is there a link? Environ Health Perspect. 2006; 114(2):156–64.
• 4. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA- Journal of the American Medical Association. 2020;323(6):548–60.
• 5. Beitz JM. Parkinson’s disease: a review. Front Biosci (Schol Ed). 2014 Jan 1; 6(1):65–74.
• 6. Ceccatelli S. Mechanisms of neurotoxicity and implications for neurological disorders. J Intern Med. 2013; 273(5):426–8.
• 7. Stricker SH, Götz M. DNA-Methylation: Master or Slave of Neural Fate Decisions? Front Neurosci. 2018; 12(2).
• 8. Schaffner SL, Kobor MS. DNA methylation as a mediator of genetic and environmental influences on Parkinson’s disease susceptibility: Impacts of alpha-Synuclein, physical activity, and pesticide exposure on the epigenome. Front Genet. 2022;13.
• 9. Feng Y, Jankovic J, Wu YC. Epigenetic mechanisms in Parkinson’s disease. J Neurol Sci. 2015; 349(1–2):3–9.
• 10. Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL. MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review. Front Neurosci. 2021;15.
• 11. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, et al. MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord. 2015; 30(12):1591–601.
• 12. Tysnes OB, Storstein A. Epidemiology of Parkinson’s disease. J Neural Transm (Vienna). 2017; 124(8):901–5.
• 13. Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019; 18(12):1091–102.
• 14. Day JO, Mullin S. The Genetics of Parkinson’s Disease and Implications for Clinical Practice. Genes (Basel). 2021; 12(7).
• 15. Selvaraj S, Piramanayagam S. Impact of gene mutation in the development of Parkinson’s disease. Genes Dis. 2019; 6(2):120–8.
• 16. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997; 276(5321):2045–7.
• 17. Blauwendraat C, Nalls MA, Singleton AB. The genetic architecture of Parkinson’s disease. Lancet Neurol. 2020; 19(2):170–8.
• 18. Bellou V, Belbasis L, Tzoulaki I, Evangelou E, Ioannidis JPA. Environmental risk factors and Parkinson’s disease: An umbrella review of meta-analyses. Parkinsonism Relat Disord. 2016; 23:1–9.
• 19. Rathore AS, Birla H, Singh S Sen, Zahra W, Dilnashin H, Singh R, et al. Epigenetic Modulation in Parkinson’s Disease and Potential Treatment Therapies. Neurochem Res. 2021; 46(7):1618–26.
• 20. Huang M, Bargues-Carot A, Riaz Z, Wickham H, Zenitsky G, Jin H, et al. Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson’s Disease. Int J Mol Sci. 2022; 23(18).
• 21. Marques SCF, Oliveira CR, Pereira CMF, Outeiro TF. Epigenetics in neurodegeneration: a new layer of complexity. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35(2):348–55.
• 22. Angelopoulou E, Paudel YN, Papageorgiou SG, Piperi C. Environmental Impact on the Epigenetic Mechanisms Underlying Parkinson’s Disease Pathogenesis: A Narrative Review. Brain Sci. 2022; 12(2).
• 23. Karakaidos P, Karagiannis D, Rampias T. Resolving DNA Damage: Epigenetic Regulation of DNA Repair. Molecules. 2020; 25(11).
• 24. Rasheed M, Liang J, Wang C, Deng Y, Chen Z. Epigenetic Regulation of Neuroinflammation in Parkinson’s Disease. Int J Mol Sci. 2021; 22(9).
• 25. Sriram K, Matheson JM, Benkovic SA, Miller DB, Luster MI, O’Callaghan JP. Deficiency of TNF receptors suppresses microglial activation and alters the susceptibility of brain regions to MPTP-induced neurotoxicity: role of TNF-alpha. FASEB J. 2006; 20(6):670–82.
• 26. Ridler C. Neuroimmunology: Microglia-induced reactive astrocytes-toxic players in neurological disease? Nat Rev Neurol. 2017 Mar 1;13(3):127.
• 27. Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature. 2017; 541(7638):481–7. /
• 28. Tang Y, Li T, Li J, Yang J, Liu H, Zhang XJ, et al. Jmjd3 is essential for the epigenetic modulation of microglia phenotypes in the immune pathogenesis of Parkinson’s disease. Cell Death & Differentiation 2014 21:3. 2013; 21(3):369–80. 29. Kumar S, Chinnusamy V, Mohapatra T. Epigenetics of Modified DNA Bases: 5-Methylcytosine and Beyond. Front Genet. 2018; 9. 30. Renani PG, Taheri F, Rostami D, Farahani N, Abdolkarimi H, Abdollahi E, et al. Involvement of aberrant regulation of epigenetic mechanisms in the pathogenesis of Parkinson’s disease and epigenetic-based therapies. J Cell Physiol. 2019; 234(11):19307–19.