Deneysel Parkinson Hastalığı Hayvan Modelleri
Özet
Parkinson hastalığı (PH), substansiya nigra pars kompaktadaki dopaminerjik nöronların kaybı ve Lewy cisimcikleriyle karakterize, motor ve motor olmayan belirtiler gösteren ilerleyici bir nörodejeneratif bozukluktur. Hastalığın patofizyolojisini anlamak ve tedavi stratejileri geliştirmek amacıyla hayvan modelleri kullanılmaktadır; bu kapsamda genetik, transkripsiyon faktörü ve nörotoksin temelli üç ana yaklaşım mevcuttur. Bu metin, PH’nin motor ve motor olmayan semptomlarını taklit etmede sıklıkla tercih edilen 6-OHDA, MPTP, parakuat/maneb ve rotenon gibi nörotoksin modellerini ele almaktadır. 6-OHDA, kan-beyin bariyerini geçemediği için stereotaktik enjeksiyon gerektirirken, unilateral modellerle motor bozuklukları başarıyla yansıtır. Lipofilik bir bileşik olan MPTP, sistemik uygulanabilmekte ve farelerde inflamasyon ile dopaminerjik hücre ölümünü taklit etmektedir. Pestisit modellerinden parakuat/maneb, Lewy cisimcikleri benzeri protein agregasyonunu indükleme avantajına sahipken; rotenon ise hücresel taşıyıcılardan bağımsız olarak tüm hücrelere girebilmekte ve Parkinson’un multisistemik dejeneratif doğasını en iyi şekilde yansıtmaktadır. Her modelin kendine özgü avantajları, yüksek mortalite veya düşük tekrarlanabilirlik gibi dezavantajları bulunmakta ve hiçbiri hastalığın tüm özelliklerini tek başına karşılayamamaktadır. Bu nedenle, deneysel çalışmalarda test edilecek hipoteze en uygun nörotoksin modelinin seçilmesi, nöroprotektif tedavilerin geliştirilmesi ve PH patogenezinin aydınlatılması açısından kritik bir önem taşımaktadır.
Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies, presenting both motor and non-motor symptoms. Animal models are utilized to comprehend the pathophysiology of the disease and to develop therapeutic strategies, encompassing three main approaches: genetic, transcription factor, and neurotoxin-based strategies. This text focuses on neurotoxin models, such as 6-OHDA, MPTP, paraquat/maneb, and rotenone, which are frequently preferred to mimic the motor and non-motor symptoms of PD. Since 6-OHDA cannot cross the blood-brain barrier, it requires stereotactic injection, yet it successfully reflects motor deficits through unilateral models. MPTP, a lipophilic compound, can be administered systemically and replicates inflammation and dopaminergic cell death in mice. Among the pesticide models, paraquat/maneb offers the advantage of inducing Lewy body-like protein aggregation, whereas rotenone can enter all cells independently of cellular transporters, thus best reflecting the multisystemic degenerative nature of Parkinson's disease. Each model possesses distinct advantages along with disadvantages like high mortality or low reproducibility, and none can completely replicate all features of the disease. Therefore, selecting the most appropriate neurotoxin model for the hypothesis to be tested in experimental studies is of critical importance for developing neuroprotective treatments and elucidating PD pathogenesis.
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