Golomidov Ilia M, Latypova Evgenia M, Ryabova Elena V, Bolshakova Olga I, Komissarov Artem E, Sarantseva Svetlana V
Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia.
J Neurogenet. 2022 Mar;36(1):1-10. doi: 10.1080/01677063.2022.2064462. Epub 2022 Apr 25.
Parkinson's disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of α-synuclein, which plays a critical role in the pathophysiology of PD. The α-synuclein is encoded by the gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in α-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human gene in over specific times employing a temperature-dependent system allows for the evaluation of neurodegenerative processes. In this study, was expressed only in the adult stage of development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly's life. It was demonstrated that the level of pathology significantly depends on the duration of α-synuclein expression. gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of α-synuclein in the brain. Importantly, repression of α-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the α-synuclein expression was blocked. Thus, we suggest that reduction of α-synuclein expression alone contributes to slowing down the development of PD-like symptoms.
帕金森病（PD）是一种神经退行性疾病，其特征是路易小体的形成以及黑质中多巴胺能（DA）神经元的逐渐丧失。路易小体主要由α-突触核蛋白组成，它在帕金森病的病理生理学中起关键作用。α-突触核蛋白由该基因编码，是首个被鉴定出与遗传性帕金森病相关的基因。目前，α-突触核蛋白中至少有六种与疾病相关的突变，这些突变会导致显性遗传的家族性帕金森病形式。利用温度依赖性系统在特定时间内对果蝇进行人该基因的靶向表达，可用于评估神经退行性过程。在本研究中，该基因仅在果蝇发育的成年阶段表达1或2周，随后在果蝇的余生中抑制基因表达。结果表明，病理水平显著取决于α-突触核蛋白的表达持续时间。较长时间的该基因表达导致多巴胺能神经元死亡、多巴胺水平降低以及运动能力下降。在这种情况下，观察到的神经退行性过程与α-突触核蛋白在果蝇大脑中的积累相关。重要的是，与不溶性部分相比，α-突触核蛋白表达的抑制导致可溶性蛋白部分的消除。在α-突触核蛋白表达被阻断后，未观察到病理特征性体征的进一步显著发展。因此，我们认为仅降低α-突触核蛋白的表达有助于减缓帕金森病样症状的发展。
