35 60

Cited 0 times in

Uric acid regulates α-synuclein transmission in Parkinsonian models

Authors
 Yu Jin Shin  ;  Yeon Ju Kim  ;  Ji Eun Lee  ;  Yi Seul Kim  ;  Jung Wook Lee  ;  HyeonJeong Kim  ;  Jin Young Shin  ;  Phil Hyu Lee 
Citation
 FRONTIERS IN AGING NEUROSCIENCE, Vol.15 : 1117491, 2023-08 
Journal Title
FRONTIERS IN AGING NEUROSCIENCE
Issue Date
2023-08
Keywords
Parkinson’s disease ; endocytosis ; transmission ; uric acid ; α-Syn
Abstract
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. Copyright © 2023 Shin, Kim, Lee, Kim, Lee, Kim, Shin and Lee.
Files in This Item:
T202400845.pdf Download
DOI
10.3389/fnagi.2023.1117491
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jin Young(신진영)
Lee, Ji Eun(이지은)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198058
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links