Uric acid regulates α-synuclein transmission in Parkinsonian models

Frontiers in Aging Neuroscience

Neuroscience

Jung Wook Lee¹  HyeonJeong Kim²  Yeon Ju Kim²  Jin Young Shin²  Phil Hyu Lee²  Yu Jin Shin²  Ji Eun Lee²  Yi Seul Kim² 

[1]Department of Medical Science, Catholic Kwandong University College of Medicine, Gangneung-si, Republic of Korea

[2]Department of Neurology, Yonsei University College of Medicine, Seoul, Republic of Korea

[3]Severance Biomedical Science Institute, Yonsei University, Seoul, Republic of Korea

关键词: uric acid;    α-Syn;    transmission;    endocytosis;    Parkinson’s disease;   

DOI  :  10.3389/fnagi.2023.1117491

 received in 2022-12-06, accepted in 2023-08-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

Ample evidence demonstrates that α-synuclein (α-syn) has a critical role in the pathogenesis of Parkinson’s disease (PD) with evidence indicating that its propagation from one area of the brain to others may be the primary mechanism for disease progression. Uric acid (UA), a natural antioxidant, has been proposed as a potential disease modifying candidate in PD. In the present study, we investigated whether UA treatment modulates cell-to-cell transmission of extracellular α-syn and protects dopaminergic neurons in the α-syn-enriched model. In a cellular model, UA treatment decreased internalized cytosolic α-syn levels and neuron-to-neuron transmission of α-syn in donor-acceptor cell models by modulating dynamin-mediated and clathrin-mediated endocytosis. Moreover, UA elevation in α-syn-inoculated mice inhibited propagation of extracellular α-syn which decreased expression of phosphorylated α-syn in the dopaminergic neurons of the substantia nigra leading to their increased survival. UA treatment did not lead to change in markers related with autophagolysosomal and microglial activity under the same experimental conditions. These findings suggest UA may control the pathological conditions of PD via additive mechanisms which modulate the propagation of α-syn.

【 授权许可】

Unknown   
Copyright © 2023 Shin, Kim, Lee, Kim, Lee, Kim, Shin and Lee.