Nörodejeneratif hastalıkların tedavisinde, nöronal patogeneze neden olan olayların anlaşılması ve uygun tedavilerin geliştirilmesi temel basamaktır. Nörodejeneratif hastalıkların çoğu mitokondriyal disfonksiyon ile ilişkilidir. İnsanlarda meydana gelen mitokondriyal genlerdeki mutasyonlar, altında yatan genetik nedenler ile doğru korelasyon göstermeyen bir dizi fenotipik sonuçlar meydana getirir. Birçok nörodejeneratif hastalık; lizozomların, endozomların ve otofagozomların işlevini etkileyen mutasyonlara sebep olabilir. Parkinson hastalığında mevcut tedaviler, hastalığın başlaması ve ilerlemesi için yetersiz kalmaktadır, bu sebeple hastalığın patogenezinin aydınlatılması gerekmektedir. Bu olayların aydınlatılması, bilim insanları için hâlâ zorluk teşkil etmektedir. Bu amaçla kullanılan deney hayvanları, yapılan araştırmalarda dünya çapında standart modeller sağlar. Alternatif yöntemlerin kullanımı ve hayvan sayısının azaltılması ile yeni tekniklerin geliştirilmesi gerekir. Alternatif yöntemlerin bilim dünyasına entegrasyonu ile in vivo yöntemlere olan gereksinim azalır. Dictyostelium discoideum hücre yapısı, sinyalleşme mekanizmaları, hücresel davranışları memeli hücreleri ile benzerlik göstermektedir. Genetik manipülasyona uygun dizilenmiş haploid kromozom yapısında, tek hücreli ve çok hücreli aşamaların olduğu kısa yaşam döngüsü ve fenotipik zenginliği sayesinde insanlardaki hastalıkların hücresel süreçlerini ortaya çıkarmak için basit bir modeldir. Tıp alanında yapılan D. discoideum ile ilgili çalışmaları; bakteriyel enfeksiyon, immün hücre kemotaksisi, otofajik hücre ölümü, mitokondriyal ve nörolojik bozukluklar alanlarında temel bilgiler sağlamıştır. D. discoideum, sahip olduğu proteom ile hücresel ve gelişimsel biyoloji için yeni bir bakış açısı sağlayabilecek bir model organizmadır. Bu derleme, nörodejeneratif hastalıklardan biri olan Parkinson hastalığının tanı ve tedavisinde D. discoideum modelinin kullanımı hakkında detaylı bilgi vermek için hazırlandı.
Anahtar Kelimeler: Dictyostelium discoideum; Parkinson hastalığı; nörodejeneratif hastalıklar; hayvan kullanımı alternatifleri
Comprehension the events that cause neuronal pathogenesis and developing appropriate treatments are the primary steps in the treatment of neurodegenerative diseases. Most neurodegenerative diseases are associated with mitochondrial dysfunction. Mutations in mitochondrial genes that occur in humans produce a range of phenotypic outcomes that do not correlate correctly with underlying genetic causes. Many neurodegenerative diseases can cause mutations that affect the function of lysosomes, endosomes, and autophagosomes. Current treatments in Parkinson's disease are insufficient for the onset and progression of the disease, so the pathogenesis of the disease needs to be clarified. The explanation of these events still poses a challenge for scientists. The experimental animals used for this purpose provide worldwide standard models for research. It is necessary to develop different techniques by reducing the number of animals with the use of alternative models. With the integration of alternative methods into the scientific world, the need for in vivo methods is reduced. Dictyostelium discoideum cell structure, signaling mechanisms, cellular behavior are similar to mammalian cells. It is a simple model for revealing the cellular processes of diseases in humans, due to its sequenced haploid chromosome structure, suitable for genetic manipulation, its a short life cycle with unicellular and multicellular stages, and its phenotypic richness. Surveys on D. discoideum in the field of medicine; provided basic information in the fields of bacterial infection, immune cell chemotaxis, autophagic cell death, mitochondrial and neurological disorders. D. discoideum is a model organism can provided that a new perspective for cellular and developmental biology with its proteome. This review was presented to provide detailed information about the use of the D. discoideum model in the diagnosis and treatment of Parkinson's disease, which is one of the neurodegenerative diseases.
Keywords: Dictyostelium discoideum; Parkinson's disease; neurodegenerative diseases; animal use alternatives
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