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Blocking the Thiol at Cysteine-322 Destabilizes Tau Protein and Prevents Its Oligomer Formation
journal contribution
posted on 2018-05-01, 00:00 authored by Hui Chen, Simu Liu, Shuiming Li, Jierui Chen, Jiazuan Ni, Qiong LiuAbnormal
accumulation of tau protein into oligomers contributes
to neuronal dysfunction. Reduction of tau level is potentially able
to prevent its accumulation. Here we uncover a critical role of the
free thiol at Cys-322 in determining tau stability. We found that
the application of thiol-blocking agents like NEM or MMTS blocks this
thiol, by which it destabilizes tau protein and prevents its oligomer
formation. Furthermore, we identified a tau-interacting protein, selenoprotein
W, which attenuates tau accumulation by forming disulfide linkage
between SelW Cys-37 and tau Cys-322. These findings provide a promising
strategy to prevent tau accumulation and oligomer formation.