Kolacheva Anna, Alekperova Leyla, Pavlova Ekaterina, Bannikova Alyona, Ugrumov Michael V
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 26 Vavilova Street, 119334 Moscow, Russia.
Brain Sci. 2022 Jun 14;12(6):779. doi: 10.3390/brainsci12060779.
The progressive degradation of the nigrostriatal system leads to the development of Parkinson's disease (PD). The synthesis of dopamine, the neurotransmitter of the nigrostriatal system, depends on the rate-limiting enzyme, tyrosine hydroxylase (TH). In this study, we evaluated the synthesis of dopamine during periods of neurodegradation and neuroplasticity in the nigrostriatal system on a model of the early clinical stage of PD. It was shown that the concentration of dopamine correlated with activity of TH, while TH activity did not depend on total protein content either in the SN or in the striatum. Both during the period of neurodegeneration and neuroplasticity, TH activity in SN was determined by the content of P19-TH, and in the striatum it was determined by P31-TH and P40-TH (to a lesser extent). The data obtained indicate a difference in the regulation of dopamine synthesis between DA-neuron bodies and their axons, which must be considered for the further development of symptomatic pharmacotherapy aimed at increasing TH activity.
黑质纹状体系统的渐进性退化导致帕金森病（PD）的发展。黑质纹状体系统的神经递质多巴胺的合成取决于限速酶酪氨酸羟化酶（TH）。在本研究中，我们在PD早期临床阶段的模型上评估了黑质纹状体系统神经退化和神经可塑性期间多巴胺的合成。结果表明，多巴胺浓度与TH活性相关，而TH活性在黑质（SN）或纹状体中均不依赖于总蛋白含量。在神经退化和神经可塑性期间，SN中的TH活性均由P19-TH的含量决定，而在纹状体中则由P31-TH和P40-TH（程度较轻）决定。所得数据表明多巴胺能神经元胞体及其轴突在多巴胺合成调节上存在差异，这在旨在提高TH活性的对症药物治疗的进一步发展中必须予以考虑。
