Kalsinörin Mekanizması ve Kalsinörin İnhibitörlerinin Alzheimer Hastalığının Tedavisindeki Önemi (Kalsinörin ve Alzheimer Hastalığı)

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.

Mechanism of Calcineurin and Importance of Calcineurin Inhibitors in the Treatment of Alzheimer's Disease (Calcineurin and Alzheimer's disease)

Alzheimer's disease (AD) is an untreatable age-related neurodegenerative disease characterized by progressive loss of memory. Although the exact cause(s) of AD is not well-understood, it is known that AD is associated with hyperphosphorylation of tau protein, disruption of microtubule stabilization and ion balance, development of inflammation and apoptosis. Although there are some drugs that currently being developed for the treatment of AD, they only delay the disease progression by alleviating the symptoms. The benefits of existing drugs in clinical trials and in practice are minimal and they do not provide a cure for these conditions. For this reason, studies on the particularly determination of new agents that have preventive and therapeutic potential on the AD become an important research field. There is growing amount of information from in vitro, ex vivo, and animal models, that evidence for hyperactivation of calcineurin, which is a threonine and serine protein phosphatase, in AD. This review details the evidence of calcineurin hyperactivity in AD and how calcineurin inhibitors, as a beacon of hope for treatment of AD, could manifest as memory repairment, anti-inflammation, tau dephosphorylation, and anti-apoptosisserine protein phosphatase, in AD. This review details the evidence of calcineurin hyperactivity in AD and how calcineurin inhibitors, as a beacon of hope for treatment of AD, could manifest as memory repairment, anti-inflammation, tau dephosphorylation, and anti-apoptosis.

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