品脱1
MPTP公司
熊去氧胆酸
神经保护
帕金
自噬
帕金森病
安普克
多巴胺能
氧化应激
药理学
PI3K/AKT/mTOR通路
线粒体
细胞凋亡
化学
程序性细胞死亡
线粒体通透性转换孔
细胞生物学
粒体自噬
多巴胺
生物
医学
内科学
神经科学
生物化学
蛋白激酶A
激酶
疾病
作者
Hui-Ping Qi,Dongfang Shen,Chuanhai Jiang,Huan Wang,Mingxiu Chang
标识
DOI:10.1016/j.neulet.2020.135493
摘要
Neuroprotection targeting mitochondrial dysfunction has been proposed as a potential therapeutic strategy for Parkinson’s disease (PD). Ursodeoxycholic acid (UDCA) has been shown to prevent neuronal damage; however, the role of UDCA in PD is poorly understood. This study aimed to investigate the neuroprotective effects of UDCA on PD and its underlying mechanisms. We used MPTP/MPP+-induced PD models, including MPTP-induced mice, primary cultures of mice mesencephalic neurons and MPP+-treated neuro-2a cells to examine the effects of UDCA on PD pathogenesis. The results showed that UDCA improved behavioral performance and protected dopaminergic neurons in MPTP mice. UDCA improved cell viability and decreased cell death in MPP+-treated cells. UDCA inhibited reactive oxygen species accumulation, mitochondrial membrane potential collapse, and ATP depletion in neuro-2a cells. UDCA improved movement dysfunction, ameliorated autophagic flux and alleviated apoptosis. Furthermore, UDCA could activate the AMPK/mTOR and PINK1/Parkin pathways. In conclusion, UDCA may improve PD by regulating mitochondrial function, autophagy, and apoptosis, involving AMPK/mTOR and PINK1/Parkin pathways. These results open new perspectives for pharmacological use of UDCA in PD.
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