Trimetilamin-N-Oksit’in Nörodejeneratif Hastalıklardaki Rolü
Özet
Trimetilamin N-oksit (TMAO), bağırsak mikrobiyotası tarafından kolin, L-karnitin ve betain gibi besin bileşenlerinden türetilen trimetilaminin karaciğerde flavin içeren monooksijenazlar aracılığıyla oksidasyonu sonucunda oluşan bir metabolittir. Son yıllarda TMAO, kardiyovasküler hastalıkların yanı sıra nörodejeneratif hastalıkların patogenezindeki olası rolü nedeniyle dikkat çekmektedir. Bu bölümün amacı, TMAO’nun metabolizmasını, fizyolojik işlevlerini ve nörodejeneratif hastalıklardaki etkilerini güncel literatür ışığında değerlendirmektir. Mevcut bulgular, TMAO’nun kan-beyin bariyerini geçebildiğini ve Alzheimer hastalığı, Parkinson hastalığı, amyotrofik lateral skleroz ve Huntington hastalığı gibi nörodejeneratif süreçlerde rol oynayabileceğini göstermektedir. Özellikle Alzheimer hastalığında TMAO’nun tau protein agregasyonunu artırdığı, nöroinflamasyonu tetiklediği, endoplazmik retikulum stresini güçlendirdiği ve mitokondriyal disfonksiyona katkıda bulunduğu bildirilmiştir. Ayrıca yüksek TMAO düzeylerinin bilişsel performansın azalması ve nörodejeneratif hastalıkların ilerlemesi ile ilişkili olduğu gösterilmiştir. Parkinson hastalığı ve amyotrofik lateral sklerozda bağırsak mikrobiyotası kaynaklı metabolit değişikliklerinin hastalık patogeneziyle ilişkili olabileceği düşünülmektedir. Sonuç olarak TMAO, nörodejeneratif hastalıkların tanı, prognoz ve tedavi süreçlerinde potansiyel bir biyobelirteç ve terapötik hedef olarak değerlendirilmektedir.
Trimethylamine N-oxide (TMAO) is a metabolite generated through the hepatic oxidation of trimethylamine, which is produced by the gut microbiota from dietary nutrients such as choline, L-carnitine, and betaine. In recent years, TMAO has attracted considerable attention due to its potential involvement in the pathogenesis of both cardiovascular and neurodegenerative diseases. The aim of this chapter is to evaluate the metabolism, physiological functions, and role of TMAO in neurodegenerative disorders in light of current evidence. Emerging studies indicate that TMAO can cross the blood–brain barrier and may contribute to the development and progression of several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease. In Alzheimer's disease, TMAO has been reported to promote tau protein aggregation, enhance neuroinflammation, activate endoplasmic reticulum stress pathways, and contribute to mitochondrial dysfunction. Elevated circulating TMAO levels have also been associated with cognitive decline and disease progression. Overall, TMAO represents a promising biomarker and potential therapeutic target for neurodegenerative disorders.
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