Deneysel Alzheimer Hastalığı Modelleri
Özet
Dünya çapında yaklaşık 50 milyon insanı etkileyen ve kesin bir tedavisi bulunmayan nörodejeneratif Alzheimer hastalığının (AH) patogenezini anlamak ve yeni tedavileri test etmek amacıyla çeşitli deneysel modeller geliştirilmiştir. Hastalık; hücre dışı amiloid beta (Aβ) plak birikimi, anormal fosforile tau proteinlerinin oluşturduğu nörofibriler yumaklar ve beyin atrofisi ile karakterizedir. İlgili araştırma yaklaşımları; transgenik olan ve olmayan hayvan modelleri ile in vitro doku ve hücre kültürü sistemlerini kapsamaktadır. Fareler ve sıçanlar üzerinde uygulanan mutant insan gen ekspresyonları (APP, PSEN1, Tau), 5xFAD ve 3xTg-AD gibi transgenik modeller amiloidoz ve tauopati süreçlerini başarıyla taklit etse de yaygın nörodejenerasyonu yansıtmada sınırlı kalmaktadır. Transgenik olmayan modeller arasında streptozotosin (STZ), Aβ peptid enjeksiyonları, yüksek yağlı diyetler ve kimyasal/lezyon müdahaleleri yer alırken; köpekler ve insan dışı primatlar sporadik AH’ye en yakın doğal özellikleri sunar. In vitro alanda ise hasta kaynaklı indüklenmiş pluripotent kök hücreler (iPSC) ve SH-SY5Y hücre hatları, moleküler mekanizmaları hücresel düzeyde doğrudan inceleme fırsatı verir. Mevcut modellerin hiçbiri insan AH’sini tüm yönleriyle tam olarak karşılayamadığından, araştırmanın amacına uygun spesifik modellerin seçilmesi klinik öncesi başarı için kritik önem taşımaktadır.
Various experimental models have been developed to understand the pathogenesis and test new treatments for Alzheimer's disease (AD), a neurodegenerative disorder affecting approximately 50 million people worldwide without a definitive cure. The disease is characterized by extracellular amyloid-beta (Aβ) plaque accumulation, neurofibrillary tangles formed by abnormally phosphorylated tau proteins, and brain atrophy. Relevant research approaches encompass transgenic and non-transgenic animal models, alongside in vitro tissue and cell culture systems. Transgenic models on mice and rats expressing mutant human genes (APP, PSEN1, Tau), such as 5xFAD and 3xTg-AD, successfully mimic amyloidosis and tauopathy processes but remain limited in reflecting widespread neurodegeneration. Non-transgenic models include streptozotocin (STZ), Aβ peptide injections, high-fat diets, and chemical/lesion interventions, while dogs and non-human primates offer natural features closest to sporadic AD. In the in vitro field, patient-derived induced pluripotent stem cells (iPSCs) and SH-SY5Y cell lines provide direct opportunities to investigate molecular mechanisms at the cellular level. Since no single model fully replicates all aspects of human AD, selecting specific models aligned with the research objectives is critical for preclinical success.
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