Lipit Metabolizmasının ve Apolipoproteinlerin Alzheimer Hastalığına Etkisi
Özet
Alzheimer hastalığı (AH), yaşlanma ile kendini gösteren, beyinde amyloid beta (Aβ) ve nörofibriler yumakların birikimi ile oluşan nöropatolojik bir hastalıktır. AH’de özellikle hafıza merkezi olarak bilinen hipokampus bölgesi etkilenir ve beynin işlevsel faliyetleri yavaşlar. Bu durum beyindeki hücrelerin ölümü ile sonuçlanır. AH gelişimi üzerine etkili birçok risk faktörü bulunmaktadır. Bu faktörlere örnek olarak genetik, yaş, cinsiyet ve eğitim gibi durumlar verilebilir. Lipitler beyin için önemli olan ve beynin kuru ağırlığının büyük kısmını oluşturan biyomoleküllerdir. Beyin, lipitleri glukozdan gerekli enerjiyi sağlayamadığı durumlarda kullanır. Literatürde lipit metabolizmasında görülen değişikliklerin ve apolipoproteinlerin AH gelişimini, beyin fonksiyonlarını ve hafızayı nasıl etkilediğini belirlemeyi amaçlayan çalışmalar mevcuttur. Bu bölümde, bu konular hakkında yapılan çalışmalar incelenmiştir. İlgili çalışmaların geneli lipit metabolizmasında görülen değişikliklerin AH ile doğrudan ilişkili olabileceğini ifade etmektedir. Kolesterolün hipokampal ve serebral kortekste birikmesi öğrenme ve hafızayı olumsuz yönde etkilemektedir. Kolesterol, AH’nin önemli faktörü olan Aβ plaklarının artmasına neden olabilir. Fakat kolesterolün AH’nin gelişimine olan etkileri yaşa ve doza bağlı olarak değişebilmektedir. Lipoproteinler, lipitlerin vücutta taşınmasını sağlayan moleküllerdir. Apolipoprotein E4 (ApoE4) içeren lipoproteinler AH için önemli genetik risk faktörleri arasında gösterilmektedir. Ayrıca ApoE4’ün yapısında görülen bir mutasyon AH’nin görülme olasılığını artırmaktadır. Lipit metabolizmasının ve apolipoproteinlerin AH’nin patofizyolojisinde rolü önemlidir ve bu konu hakkında net sonuçların elde edilebilmesi için daha fazla çalışmanın yapılmasına ihtiyaç duyulmaktadır.
Alzheimer's disease (AD) is a neuropathological disease that manifests with aging and occurs with the accumulation of amyloid beta (Aβ) and neurofibrillary tangles in the brain. In AD, the hippocampus region, known as the memory center, is especially affected, and the functional activities of the brain slow down. This condition results in the death of cells in the brain. There are many risk factors that affect the development of AD. Examples of these factors include genetics, age, gender, and education. Lipids are biomolecules that are important for the brain and make up most of the brain's dry weight. The brain uses lipids in cases where it cannot provide the necessary energy from glucose. There are studies in the literature aiming to determine how changes in lipid metabolism and apolipoproteins affect the development of AD, brain functions, and memory. In this chapter, studies on these issues are examined. The majority of relevant studies show that changes in lipid metabolism are directly related to AD. Accumulation of cholesterol in the hippocampal and cerebral cortex negatively affects learning and memory. Cholesterol can cause an increase in Aβ plaques, which are an important factor in AD. However, the effects of cholesterol on the development of AD vary depending on age and dose. Lipoproteins are molecules that allow lipids to be transported throughout the body. Apolipoprotein E4 (ApoE4)-containing lipoproteins are shown to be significant genetic risk factors for Alzheimer's disease. In addition, a mutation in the structure of ApoE4 increases the possibility of AD. The role of lipid metabolism and apolipoproteins in the pathophysiology of AD is important, and more studies are needed to obtain clear results on this subject.
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Referanslar
Husain M. Schott JM. (Ed). Oxford textbook of cognitive neurology and dementia. Oxford University Press. 2016.
Chew H, Solomon VA, Fonteh AN. Involvement of Lipids in Alzheimer's Disease Pathology and Potential Therapies. Front Physiol. 2020;9(11):598. doi: 10.3389/fphys.2020.00598
Ann Dipika Binosha Fernando, WM, Rainey‐Smith SR, Martins IJ, et al. In Vitro Study to Assess the Potential of Short Chain Fatty Acids (SCFA) as Therapeutic Agents for Alzheimer's Disease. Alzheimer's & Dementia, 2014; 10, 626.
Dinkova-Kostova AT, Kostov RV. Glucosinolates and isothiocyanates in health and disease. Trends Mol Med. 2012;18(6):337-47. doi: 10.1016/j.molmed.2012.04.003
Lei E, Vacy K, Boon WC. Fatty acids and their therapeutic potential in neurological disorders. Neurochem Int. 2016;95:75-84. doi: 10.1016/j.neuint.2016.02.014
Bianca Velasco A, Tan ZS. Fatty Acids and the Aging Brain. In: Watson RR, De Meester F, (ed). Omega-3 Fatty Acids in Brain and Neurological Health., Elsevier; 2014 p. 201–19.
Hooijmans CR, Kiliaan AJ. Fatty acids, lipid metabolism and Alzheimer pathology. Eur J Pharmacol. 2008;6,585(1):176-96. doi: 10.1016/j.ejphar.2007.11.081
Sultana R, Perluigi M, Butterfield DA. Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer's disease: insights into mechanism of neurodegeneration from redox proteomics. Antioxid Redox Signal. 2006;8(11-12):2021-37. doi: 10.1089/ars.2006.8.2021
Esterbauer H, Schaur RJ, Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 1991;11(1):81-128. doi: 10.1016/0891-5849(91)90192-6
Markesbery WR. Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 1997;23(1):134-47. doi: 10.1016/s0891-5849(96)00629-6
Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging. 2014;35,2:S59-64. doi: 10.1016/j.neurobiolaging.2014.03.038
Naqvi AZ, Harty B, Mukamal KJ, et al. Monounsaturated, trans, and saturated Fatty acids and cognitive decline in women. J Am Geriatr Soc. 2011;59(5):837-43. doi: 10.1111/j.1532-5415.2011.03402.x
Takechi R, Galloway S, Pallebage-Gamarallage MM, et al. Dietary fats, cerebrovasculature integrity and Alzheimer's disease risk. Prog Lipid Res. 2010;49(2):159-70. doi: 10.1016/j.plipres.2009.10.004
Schaefer EJ, Bongard V, Beiser AS, et al. Plasma phosphatidylcholine docosahexaenoic acid content and risk of dementia and Alzheimer disease: the Framingham Heart Study. Arch Neurol. 2006;63(11):1545-50. doi: 10.1001/archneur.63.11.1545
Florent-Béchard S, Desbène C, Garcia P, et al. The essential role of lipids in Alzheimer's disease. Biochimie. 2009;91(6):804-9. doi: 10.1016/j.biochi.2009.03.004
Hooijmans CR, Van der Zee CE, Dederen PJ,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. doi: 10.1016/j.nbd.2008.12.002
Lim GP, Calon F, Morihara T, 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;23;25(12):3032-40. doi: 10.1523/JNEUROSCI.4225-04.2005
Oster T, Pillot T. Docosahexaenoic acid and synaptic protection in Alzheimer's disease mice. Biochim Biophys Acta. 2010;1801(8):791-8. doi: 10.1016/j.bbalip.2010.02.011
Wu A, Ying Z, Gomez-Pinilla F. The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci. 2004;19(7):1699-707. doi: 10.1111/j.1460-9568.2004.03246.x
Morris MC, Evans DA, Tangney CC, et al. Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol. 2006;63(8):1085-8. doi: 10.1001/archneur.63.8.1085
Pistell PJ, Morrison CD, Gupta S, et al. Cognitive impairment following high fat diet consumption is associated with brain inflammation. J Neuroimmunol. 2010;26;219(1-2):25-32. doi: 10.1016/j.jneuroim.2009.11.010
Park HR, Park M, Choi J, et al. A high-fat diet impairs neurogenesis: involvement of lipid peroxidation and brain-derived neurotrophic factor. Neurosci Lett. 2010;4;482(3):235-9. doi: 10.1016/j.neulet.2010.07.046
Zhang X, Dong F, Ren J, et al. High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Exp Neurol. 2005;191(2):318-25. doi: 10.1016/j.expneurol.2004.10.011
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