Deneysel Parkinson Modelleri
Özet
Parkinson hastalığı (PD), geniş bir motor ve motor dışı semptom yelpazesiyle karakterize olan ilerleyici bir nörodejeneratif bozukluktur ve mevcut tedavi yaklaşımları yalnızca semptomatik iyileşme sağlamakta, hastalığın ilerleyişini değiştirememektedir. Son yıllarda PD’nin mekanistik temellerini aydınlatmak ve potansiyel terapötik müdahaleleri değerlendirmek amacıyla çok sayıda hayvan modeli geliştirilmiştir. Bu modeller; farmakolojik ajanlar, nörotoksinler, pestisitler, genetik manipülasyonlar, α-sinüklein aşılaması ve viral vektör aracılı gen aktarımı gibi çeşitli yöntemlerle oluşturulmaktadır. Her ne kadar hiçbir model PD’nin tam klinik ve patolojik özelliklerini bütünüyle yeniden oluşturamasa da, motor ve motor dışı fenotiplerin belirli yönlerini taklit ederek hastalığın biyolojik mekanizmalarına ilişkin kritik bilgiler sağlamaktadırlar. Kemirgenler, insan dışı primatlar ve Drosophila melanogaster ile Caenorhabditis elegans gibi memeli olmayan organizmalar dahil olmak üzere geniş bir tür yelpazesinde geliştirilen bu modeller, hem klasik hem de daha az çalışılmış deneysel paradigmaları kapsamaktadır. Ayrıca, bu modeller PD’nin birincil patojenik özelliklerinin yanı sıra mitokondriyal bozulma, otofajik disfonksiyon ve nöroinflamasyon gibi ikincil patolojik süreçlerin incelenmesine de olanak tanımaktadır. Bu derleme, Parkinson hastalığı araştırmalarında kullanılan geleneksel ve geleneksel olmayan hayvan modellerine ilişkin kapsamlı ve güncel bir genel bakış sunmayı ve araştırmacıların kendi bilimsel sorularına en uygun modeli seçmelerine rehberlik etmeyi amaçlamaktadır.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by a wide spectrum of motor and non-motor symptoms, and current therapeutic approaches remain limited to symptomatic relief without modifying disease progression. Over recent decades, numerous animal models have been developed to elucidate the mechanistic basis of PD and to evaluate potential therapeutic interventions. These models are generated through pharmacological agents, neurotoxins, pesticides, genetic manipulations, α-synuclein inoculation, and viral vector–mediated gene delivery. Although none of these models fully recapitulates the complete pathological and clinical profile of PD, they successfully mimic distinct motor and non-motor phenotypes, thereby providing critical insights into disease mechanisms. A broad range of species—including rodents, non-human primates, and non-mammalian organisms such as Drosophila melanogaster and Caenorhabditis elegans—have been utilized, encompassing both well-established and underexplored experimental paradigms. In addition to replicating primary pathogenic features, these models permit the investigation of secondary pathological processes such as mitochondrial impairment, autophagic dysfunction, and neuroinflammation. This review aims to offer a comprehensive and up-to-date overview of conventional and unconventional PD animal models and to guide researchers in selecting the most appropriate model tailored to their specific scientific objectives.
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