ALZHEİMER HASTALIĞI ÜZERİNE FLAVONOİDLERİN ETKİSİ

Alzheimer hastalığı sıklığı giderek artan nörodejeneratif bir hastalıktır. Hastalığın oluşumu ve ilerlemesinde genetik, oksidatif stres, inflamasyon, amiloid beta peptid (Aβ), mitokondrial disfonksiyon etkili olmaktadır. Bu hastalığın gelişiminde amiloid beta (Aβ) ve tau proteinlerinin hiperfosforilasyonu rol oynamaktadır. Amiloid beta (Aβ) üretiminin artması sonucu amiloid plaklar oluşmakta ve plak birikimi görülmektedir. Amiloid plak birikimi ve tau proteininin hiperfosforilasyonu nöral hücre hasarı oluşumuna yol açmaktadır. Oksidatif stres, Alzheimer hastalığı gibi pekçok nörodejeneratif hastalık sürecinde etkili olmakta ve prognozun kötüleşmesine yol açabilmektedir. Oksidatif stres oksidan ve antioksidan ögeler arasındaki dengenin bozulması sonucu oluşmaktadır. Bu dengesizlik sonucunda reaktif oksijen cisimleri (ROS) miktarı artmakta ve hücre ölümleri ortaya çıkabilmektedir. Alzheimer hastalığı ile ilişkili bir diğer durum nöroinflamasyondur. Kronik olarak artmış inflamatuar sitokin seviyesi, nöronal yaralanmaya yardımcı olmaktadır. Beyinde inflamatuar sitokin üretiminin artması, davranış değişikliklerine ve nörotoksisitenin desteklenmesine neden olabilmektedir. Flavanoidlerin Alzheimer hastalığına karşı koruyucu ve ilerlemesini önleyici etkileri bulunmaktadır. Flavanoidler, beyindeki immün sistemi değiştirebilmekte, sitokin ve nitrik oksit üretimini inhibe ederek nöroinflamasyonu azaltabilmektedir. Flavanoidlerin antiinflamatuar etkisi TNF-α ve IL-1β dahil inflamatuar sitokinlerin mikroglial aktivasyonunun inhibe edilmesi; glia aktivasyona cevap olarak indüklenebilir nitrik oksit sentaz (iNOS) uyarılmasının ve bunun sonucunda nitrik oksit üretiminin inhibe edilmesi; NADPH oksidaz aktivasyonunun ve bunun sonucunda raktif oksijen cisimleri (ROS) üretiminin inhibe edilmesi; nöronal sinyal yolları ve glia modülasyonu aracılığıyla NF-κB gibi proinflamatuar transkripsiyon faktörlerinin aktivitesinin düşürülmesinden kaynaklanmaktadır. Sonuç olarak flavanoidler Alzheimer hastalığından korunmada ve ilerlemesinin yavaşlatılmasında önemli etkilere sahiptir. Polifenollerden zengin beslenme planının Alzheimer hastalığının tedavisine destek olarak kullanılması, hastalığın prognozunun iyileşmesine katkı sağlayabilecektir.

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