Decreasing the intrinsically disordered protein α-synuclein levels by targeting its structured mRNA with a ribonuclease-targeting chimera

Tong, Yuquan; Zhang, Peiyuan; Yang, Xueyi; Liu, Xiaohui; Zhang, Jie; Grudniewska, Magda; Jung, Ikrak; Abegg, Daniel; Liu, Jun; L. Childs‐Disney, Jessica; M. R. Gibaut, Quentin; S. Haniff, Hafeez; Adibekian, Alexander; Maral Mouradian, M.; D. Disney, Matthew

doi:10.1073/pnas.2306682120

Public

Decreasing the intrinsically disordered protein α-synuclein levels by targeting its structured mRNA with a ribonuclease-targeting chimera

Published in Proceedings of the National Academy of Sciences • Jan 5, 2024

Authors:

Yuquan Tong

Peiyuan Zhang

Xueyi Yang

Abstract

α-Synuclein is an important drug target for the treatment of Parkinson’s disease (PD), but it is an intrinsically disordered protein lacking typical small-molecule binding pockets. In contrast, the encoding SNCA mRNA has regions of ordered structure in its 5′ untranslated region (UTR). Here, we pres...

Subject

Messenger RNA

Druggability

Untranslated region

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