Çöpçü Reseptörler ve Hastalıklarla İlişkisi
Özet
Çöpçü reseptörler (ÇR), 1970'li yıllarda makrofajlarda okside olmuş LDL'yi bağlama yetenekleriyle keşfedilen ve günümüzde protein yapıları ile bağlanma bölgelerine göre A-J arasında 10 farklı sınıfa ayrılan zara bağlı bir reseptör süper ailesidir. Bu reseptör ailesinin üyeleri lipoproteinler, kolesterol esterleri, fosfolipitler, proteoglikanlar, ferritin, karbonhidratlar, patojenik yapılar ve apoptotik hücreler gibi son derece geniş bir ligand yelpazesini bağlayarak endositoz, fagositoz ve hücresel bağışıklık süreçlerinde aktif rol oynarlar. Fizyolojik işlevlerinin yanı sıra; ateroskleroz, insülin direnci, diyabet, kanser, obezite, metabolik sendrom, alkol dışı karaciğer yağlanması ve Alzheimer hastalığı gibi çeşitli patolojik durumlarda kritik etkileri bulunmaktadır. Ateroskleroz gelişiminde oxLDL'nin makrofajlarca tutulmasını ve köpük hücre oluşumunu tetikleyerek plak birikimini artırmakta; insülin direnci ve diyabette ise enflamatuvar sitokinlerin salınımı ve endoplazmik retikulum stresi üzerinden insülin sinyal yollarını bozarak doku duyarsızlaşmasına neden olmaktadırlar. Kanser patolojisinde ise tümör hücrelerinin adezyonu, metastatik potansiyeli, anjiyogenez ve anti-tümör bağışıklık yanıtlarının düzenlenmesinde görev alırlar. Hücresel sinyal yollarında kritik roller üstlenen bu reseptörlerden özellikle CD36, CD68, CD206 ve LOX-1 gibi üyelerin yakın gelecekte söz konusu hastalıkların tanı ve tedavisinde klinik kullanımları muhtemel görülmektedir.
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