Kalsinörin Mekanizması ve Kalsinörin İnhibitörlerinin Alzheimer Hastalığının Tedavisindeki Önemi

Year 2017, Volume: 24 Issue: 4, 178 - 187, 01.12.2017

Fatma Gonca Koçancı , Belma Aslım

https://doi.org/10.17343/sdutfd.263872

Abstract

Alzheimer hastalığı (AH), hafızanın sürekli bir şekilde azalması ile karakterize olan, tedavi edilemeyen, yaşa bağlı nörodejeneratif bir hastalıktır. AH’nin nedenleri tam olarak açıklanamamış olsa da, tau proteinlerinin hiperfosforilasyonunun, mikrotübül stabilizasyonun ve iyon dengesinin bozulmasının, inflamasyon oluşumunun ve apoptozun AH ile ilişkili olduğu bilinmektedir. AH tedavisi için hali hazırda geliştirilen ilaçlar olmasına rağmen, bunlar ancak semptomları yavaşlatarak hastalığın ilerlemesini geciktirmektedir. Mevcut ilaçların klinik çalışmalarda ve pratikte yararları minimaldir ve hiçbiri tam anlamıyla bir tedavi sağlayamamaktadır. Bu nedenle, AH üzerinde etkili olacak koruyucu ve tedavi edici potansiyeli olan yeni ajanların belirlenme çalışmaları önemli bir araştırma alanı haline gelmiştir. Bir treonin ve serin protein fosfataz olan kalsinörinin, AH’de hiperaktivasyonunu kanıtlayan in vitro, ex vivo ve hayvan modellerine ilişkin bilgiler giderek artmaktadır. Bu derleme, kalsinörin mekanizmasını, AH’de görülen kalsinörinin hiperaktivitesine ait kanıtları ve AH tedavisinde bir umut ışığı olarak kalsinörin inhibitörlerinin bellek onarımında, anti-inflamasyonda, tau defosforilasyonunda ve anti-apoptozda nasıl etki ettiğine dair ayrıntıları içermektedir.

Keywords

Alzheimer hastalığı, kalsinörin, kalsinörin inhibitörleri

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