Apoptotik Yolaklar ve Hedefe Yönelik Tedaviler

Yıl 2020, Cilt: 27 Sayı: 4, 565 - 573, 25.12.2020

Aylin Gökhan , Kubilay Doğan Kılıç , Kanat Gülle Yiğit Uyanıkgil , Türker Çavuşoğlu

https://doi.org/10.17343/sdutfd.619417

Öz

Fizyolojik ve patolojik durumlarda, işleyişleri farklı, nekroz ve apoptoz olarak adlandırılan iki ana hücre ölümü meydana gelir. Apoptoz basamaklarındaki disregülasyonun kanser veya otoimmüniteyi tetiklediği bildirilmiş olup, aşırı apoptoz ise dejeneratif hastalıklarla ilişkilendirilmektedir. Proliferasyon artışıyla karakterize edilen kanserin tedavisi için hücrelerin apoptozdan kurtulma yolları araştırılmaktadır. Bununla ilişkili olarak kanser hücrelerinde Bcl-2, Bcl-xL ve Mcl-1 gibi antiapoptotik proteinlerin arttığı, proapoptotik proteinlerin ise azaldığı belirlenmiştir. Hücre ölümünde görev alan birçok protein ve protein kompleksleri arasında bir diğer önemli grubu apoptoz inhibitörü (IAP) protein ailesi oluşturmaktadır. IAP’lar apoptozda hem intrinsik hem de ekstrinsik yolağı baskılayabilen endojen kaspaz inhibitörleri olarak fonksiyon görmekte olup, apoptoz dışında hücre bölünmesi ve immün regülasyonda da rol almaktadırlar. Bcl-2 ve IAP ailesi üyeleri gibi aşırı ekspresyonu tespit edilen proteinler, hem tanı koyma hem de tedavi aşamasında yarar sağlamaktadır. Günümüzde sadece kanser hücresini hedefleyen ilaçlar tedavi protokolleri arasına girmiş bulunmaktadır. Bu derlemede apoptotik yolaklara ait moleküler mekanizmalar ve onlarla ilişkili hedefe yönelik yeni tedavi yaklaşımları genel hatlarıyla irdelenmektedir.

Anahtar Kelimeler

Apoptoz, Bcl-2, Apoptoz İnhibitörü Proteinler, Hedefe Yönelik Tedavi

Kaynakça

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