Nörodejeneratif hastalıklardan biri olan Alzheimer hastalığı (AH), günümüzde yaygın olarak görülen ve hafıza kaybı, bilişsel işlevlerde bozulma ve ilerleyen zamanlarda günlük aktiviteleri yerine getirememeyle kendini gösteren bir demans türüdür. Sadece palyatif tedavisi olan bu hastalıkta, beyinde kademeli olarak artan ve geri dönüşümü olmayan bir hasar meydana gelmektedir. Bu hastalığın etiyolojini araştırmak için son yıllarda çok sayıda in vitro ve in vivo model geliştirilmektedir. Araştırmacılar, hayvan modelleri ile AH'nin lezyonlarını, semptomlarını veya nedenlerini taklit etmeye çalışmaktadır. AH üzerine yapılan araştırmalarda, hayvan kullanmanın çeşitli avantajları bulunmaktadır. AH hayvan modelleri geliştirilirken, hastalıkta 'amiloid plak' ve 'nörofibriler yumakların' birikimi olduğu için 'βamiloid' ve 'Tau proteini' modelleri üzerine odaklanılmıştır. Bu farklı modeller, araştırıcıların manipülasyon yeteneklerini artırabilmektedir. Ayrıca deney hayvanlarının yaşam süresi kısa olduğu için modeli oluşturmak ve sonuçlarını görmek hızlı bir şekilde gerçekleşebilmektedir ve kararlı laboratuvar koşulları, çevresel ve fizyolojik etmenlerin etkisini azaltmaktadır. Hayvanlardaki fizyolojik değişiklikler de daha yakından izlenebilmektedir. Ancak bu modeller, AH'nin temel özelliklerini ortaya çıkarsa da hiçbiri insan beyninde gözlenen patolojik özellikleri tam olarak taklit etmemektedir. Geliştirilen AH modelleri, genel olarak 'transgenik' ve 'transgenik olmayan' hayvanlar üzerinde yapılmaktadır. Transgenik hayvan modeli olarak, çalışmaların büyük bir kısmında fareler kullanılmaktadır. Bu geleneksel derlemede, AH araştırmalarında kullanılan in vivo modelleri olan Tg2576, APP23, PDAPP, PSEN1, JNPL3 ve TAPP fare modelleri hakkında güncel bilgiler özetlenmiş ve bu modellerin üstünlükleri ve dezavantajları tartışılmıştır.
Anahtar Kelimeler: Alzheimer hastalığı; hayvan modelleri; Tau; amiloid beta; nörofibriler yumak
Alzheimer's disease (AD), a neurodegenerative disease, is a common dementia that presents itself with memory loss, deterioration in cognitive functions and inability to perform daily activities in the future. In this disease, which has only palliative treatment, gradual increase and irreversible damage in the brain occurs. Numerous in vitro and in vivo models have been developed in recent years to investigate the etiology of the disease. Researchers are trying to mimic the lesions, symptoms or causes of AD with animal models. There are several advantages of using animals in research on AD. Animal models of AD have focused on 'β-amyloid' and 'Tau protein' models because of the accumulation of 'amyloid plaque' and 'neurofibrillary tangles' in the disease. These different models can increase manipulation abilities of researchers. In addition, since life span of experimental animals is short, creating the model and seeing the results can be faster and under stable laboratory conditions, effects of environmental and physiological factors can be reduced. Physiological changes in animals can also be monitored more closely. However, although these models reveal basic features of AD, none of them fully mimic the pathological features observed in the human brain. Developed AD models are generally performed on 'transgenic' and 'nontransgenic' animals. Mice are used in the majority of transgenic animal models. In this traditional review, up-to-date information about Tg2576, APP23, PDAPP, PSEN1, JNPL3 and TAPP mouse models, which are in vivo models used in AD research, are compiled and advantages and disadvantages of these models are discussed.
Keywords: Alzheimer's disease; animal models; Tau; amyloid beta; neurofibrillary tangle
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