Ursodeoxycholic acid protects dopaminergic neurons from oxidative stress via regulating mitochondrial function, autophagy, and apoptosis in MPTP/MPP+-induced Parkinson's disease. (10th January 2021)

• Record Type: Journal Article
• Authors: Qi, Huiping; Shen, Dongfang; Jiang, Chenggong; Wang, Huan; Chang, Mingxiu
• Is Part Of: Neuroscience letters. Volume 741(2021)
• Publication Date: 2021-01-10
• Subjects: UDCA -- Parkinson's disease -- Mitochondrial dysfunction -- Autophagy -- Apoptosis -- MPTP/MPP+; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2020.135493
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: UDCA promotes motor symptoms and protects dopaminergic neurons in PD models. UDCA ameliorates mitochondrial function, autophagy, and apoptosis. UDCA activates AMPK/mTOR/ULK1 and PINK1/Parkin pathways. Abstract: 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.