Back to Search Start Over

Phosphorylation of α-synuclein at T64 results in distinct oligomers and exerts toxicity in models of Parkinson's disease.

Authors :
Hideaki Matsui
Shinji Ito
Hideki Matsui
Junko Ito
Gabdulkhaev, Ramil
Mika Hirose
Tomoyuki Yamanaka
Akihide Koyama
Taisuke Kato
Maiko Tanaka
Norihito Uemura
Noriko Matsui
Sachiko Hirokawa
Maki Yoshihama
Aki Shimozawa
Shin-ichiro Kubo
Kenji Iwasaki
Masato Hasegawa
Ryosuke Takahashi
Keisuke Hirai
Source :
Proceedings of the National Academy of Sciences of the United States of America; 6/6/2023, Vol. 120 Issue 23, p1-8, 44p
Publication Year :
2023

Abstract

α-Synuclein accumulates in Lewy bodies, and this accumulation is a pathological hallmark of Parkinson's disease (PD). Previous studies have indicated a causal role of α-synuclein in the pathogenesis of PD. However, the molecular and cellular mechanisms of α-synuclein toxicity remain elusive. Here, we describe a novel phosphorylation site of α-synuclein at T64 and the detailed characteristics of this post-translational modification. T64 phosphorylation was enhanced in both PD models and human PD brains. T64D phosphomimetic mutation led to distinct oligomer formation, and the structure of the oligomer was similar to that of α-synuclein oligomer with A53T mutation. Such phosphomimetic mutation induced mitochondrial dysfunction, lysosomal disorder, and cell death in cells and neurodegeneration in vivo, indicating a pathogenic role of α-synuclein phosphorylation at T64 in PD. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
120
Issue :
23
Database :
Complementary Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
164319717
Full Text :
https://doi.org/10.1073/pnas.2214652120