Alzheimer Hastalığı’nda In Vivo ve In Vitro Modeller

Year 2023, Volume: 6 Issue: 1, 54 - 77, 29.04.2023

Başak Aru , Ahmet Develioğlu , Gizem Gürel , Gülderen Yanıkkaya Demirel

https://doi.org/10.54537/tusebdergisi.1213712

Abstract

Alzheimer Hastalığı (AH), amiloid beta plaklarının ve hücre içinde hiper-fosforile mikrotübül ilişkili proteinin birikimi sonucu meydana gelen nörofibriler yumaklar ile karakterize olan geri dönüşsüz bir nörodejeneratif hastalıktır. AH, demansın temel sebebi olup 21. yüzyılda sağlık sistemine ilişkin en büyük problemlerinden biridir. Hastalık patogenezinde çevresel ve genetik faktörlerin rol oynadığı bilinmekte olup bilinen bir tedavisi yoktur. AH patolojisinin anlaşılması ve yeni terapötik yöntemlerin geliştirilmesi hususlarında deneysel AH modelleri kritik önem taşırlar. Ancak çalışmalar, temel araştırmalar sonucu elde edilen verilerin klinik çalışmalarda oldukça düşük oranda başarı gösterdiğini ifade etmektedir; dolayısıyla literatürde bulunan modellerin güçlü ve zayıf yanlarının değerlendirilmesi ve çalışmaların, hastalığın farklı yönlerini kapsayıcı modellerle gerçekleştirilmesinin potansiyel tedavilerin başarılarını artıracağı öngörülmektedir. Bu derleme makalede, farklı in vivo ve in vitro AH modellerinin patolojik ve moleküler özellikleri ele alınmış; bu bağlamda, geleneksel olarak kullanımda olan transgenik hayvan modelleri ile kanser hücrelerinin nöral farklılaştırmalarına dayalı yöntemlere ek olarak güncel hücre kültürü çalışmalarının odak noktaları olan indüklenebilir kök hücre kökenli organoid yapıları ve nöral progenitör hücre kaynaklı AH modelleri karşılaştırılmıştır. Ayrıca farklı in vivo ve in vitro AH modellerinin kullanımlarının dönüşümsel özelliklerini kısıtlayıcı etmenler, organizma bazında özetlenmiştir.

Keywords

Alzheimer Hastalığı, Hayvan Modelleri, Hücre Kültürü Modelleri

In vivo and in vitro Models of Alzheimer’s Disease

Abstract

Alzheimer's Disease (AD) is an irreversible neurodegenerative disease characterized by neurofibrillary tangles resulting from the accumulation of amyloid beta plaques and hyper-phosphorylated microtubule-associated protein in the cell. It is the main cause of dementia and is one of the biggest health care problems in the 21st century. It is known that environmental and genetic factors contribute to the pathogenesis of the disease, and no known cure is available. Experimental models of AD are critical to understand the AD pathology and the development of new therapeutic modalities. However, studies indicate that the data obtained from the basic research contribute to the clinical studies with a very low success rate. Therefore, it is predicted that evaluating the strengths and weaknesses of the models in the literature and carrying out studies with models that cover different aspects of the disease will increase the success of potential treatments. In this review article, pathological and molecular features of different in vivo and in vitro AD models are discussed. In this context, in addition to traditionally used transgenic animal models and methods based on neural differentiation of cancer cells, induced stem cell-derived organoid structures and neural progenitor cell-derived AD models, which are the focus of current cell culture studies, were compared. In addition, the factors limiting the translational properties of the use of different in vivo and in vitro AD models are summarized based on organism.

Keywords

Alzheimer's Disease, Animal Models, Cell Culture Models

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