Journal
NEUROSCIENCE LETTERS
Volume 741, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2020.135493
Keywords
UDCA; Parkinson's disease; Mitochondrial dysfunction; Autophagy; Apoptosis; MPTP/MPP+
Categories
Funding
- Heilongjiang Postdoctoral Research Foundation [LBH-Z18199]
- Fundamental Research Funds for the Provincial Universities [2019-KYYWF0366]
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Neuroprotection targeting mitochondrial dysfunction with ursodeoxycholic acid (UDCA) shows potential therapeutic effects for Parkinson's disease (PD). UDCA improves motor dysfunction, protects dopaminergic neurons, and regulates autophagy and apoptosis through activating the AMPK/mTOR and PINK1/Parkin pathways. The study suggests that UDCA may have pharmacological benefits in treating PD by modulating mitochondrial function.
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 neum-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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