河北师范大学体育学院
G804.2
国家自然科学基金项目 (No.32071171) 和河北省教育厅科学研究项目(No.QN2020146) 资助
School of Physical Education,Hebei Normal University
Supported by the National Natural Science Foundation of China (No.32071171) and the Scientific Research Project of Hebei Provincial Department of Education (No.QN2020146)
帕金森病(PD)是一种神经退行性疾病,其核心特征是黑质致密部多巴胺能神经元的退行性凋亡,导致纹状体多巴胺水平的持续下降,主要表现为静止性震颤、肌强直和运动迟缓等运动功能障碍。纹状体是皮层下调控躯体运动的重要中枢,其功能受多条信号通路的精细调控。中等多棘神经元(MSNs)是纹状体内的主要神经元,其中表达多巴胺2型受体的MSNs(D2-MSNs)的功能异常与PD的运动障碍密切相关。PD患者纹状体细胞外信号调节激酶/丝裂原激活蛋白激酶(Erk/MAPK)信号通路活性发生改变,进而影响D2-MSNs的功能活动。运动干预作为PD的潜在治疗策略,已被证明可以通过抑制Erk/MAPK信号通路调控D2-MSNs功能活动。然而,Erk/MAPK信号通路在D2-MSNs运动依赖可塑性中的作用,以及对PD运动功能障碍改善的具体调控机制仍不明确。因此,本文旨在深入探讨纹状体Erk/MAPK信号通路在PD运动防治中的作用及生物学机制,以期为PD治疗新靶点的发现提供科学依据。
Parkinson"s disease (PD) is a neurodegenerative disease in which the level of DA in striatum is continuously reduced due to the apoptosis of dopaminergic neurons in the substantia densa nigra (SNpc). The main clinical manifestations are static tremor, myotonia, and bradykinesia. The striatum is an important center in the regulation of subcortical motor function, which is regulated by several signaling pathways. Medium multispinous neurons are one of the key neurons in the striate. The dopamine receptor type 2 medium multispinous neurons (D2-MSNs), which account for half of MSNs, play a key role in motor regulation. The abnormal function of D2-MSNs is thought to be related to the development of PD motor dysfunction. The extracellular signal-regulated kinase/mitogen-activated protein kinase (Erk/MAPK) signaling pathway is pathologically altered in PD, further leading to decreased D2-MSNs activity. Exercise intervention is considered as a potential therapeutic strategy for PD, and recent studies have shown that exercise can enhance the activity of D2-MSNs by inhibiting the Erk/MAPK signaling pathway. However, the specific role of Erk/MAPK signaling pathway in exercise intervention to alleviate PD motor dysfunction is still unknown. Therefore, this paper aims to explore the relationship between Erk/MAPK signaling pathway in striatal neurons and PD motor prevention and treatment, and provide scientific basis for finding new targets for PD treatment.
高 博,赖一宁,葛一彤,陈 巍.纹状体Erk/MAPK信号通路在运动改善帕金森病中的研究进展[J].生物化学与生物物理进展,,():
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