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Identification and Characterization of DNA Aptamers Specific for Phosphorylation Epitopes of Tau Protein

Author:
Teng, I-Ting, Li, Xiaowei, Yadikar, Hamad Ahmad, Yang, Zhihui, Li, Long, Lyu, Yifan, Pan, Xiaoshu, Wang, Kevin K., Tan, Weihong
Source:
Journal of the American Chemical Society 2018 v.140 no.43 pp. 14314-14323
ISSN:
1520-5126
Subject:
epitopes, microtubules, neurodegenerative diseases, nucleotide aptamers, oligomerization, phosphorylation, protein aggregates, therapeutics
Abstract:
Tau proteins are proteins that stabilize microtubules, but their hyperphosphorylation can result in the formation of protein aggregates and, over time, neurodegeneration. This phenomenon, termed tauopathy, is pathologically involved in several neurodegenerative disorders. DNA aptamers are single-stranded oligonucleotides capable of specific binding to target molecules. Using tau epitopes predisposed for phosphorylation, we identified six distinct aptamers that bind to tau at two phosphorylatable epitopes (Thr-231 and Ser-202) and to full-length Tau441 proteins with nanomolar affinity. In addition, several of these aptamers also inhibit tau phosphorylation (IT4, IT5, IT6) and tau oligomerization (IT3, IT4, IT5, IT6). This is the first report to identify tau epitope-specific aptamers. Such tau aptamers can be used to detect tau in biofluids and uncover the mechanism of tauopathy. They can be further developed into novel therapeutic agents in mitigating tauopathy-associated neurodegenerative disorders.
Agid:
6194870