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J Am Chem Soc. 2018 Oct 31;140(43):14314-14323. doi: 10.1021/jacs.8b08645. Epub 2018 Oct 16.

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

Author information

1
Department of Chemistry, Department of Physiology and Functional Genomics, Center for Research at Bio/Nano Interface, UF Health Cancer Center , UF Genetics Institute and McKnight Brain Institute, University of Florida , Gainesville , Florida 32611-7200 , United States.
2
Department of Emergency Medicine, Department of Chemistry, Department of Neuroscience, and Department of Psychiatry , McKnight Brain Institute, University of Florida , Gainesville , Florida 32611 , United States.
3
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory for Chemo/Bio-Sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, and Aptamer Engineering Center of Hunan Province , Hunan University , Changsha 410082 , China.
4
Brain Rehabilitation Research Center (BRRC) , Malcom Randall Veterans Affairs Medical Center , 1601 SW Archer Road , Gainesville Florida 32608 , United States.

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.

PMID:
30277395
PMCID:
PMC6442731
[Available on 2019-10-31]
DOI:
10.1021/jacs.8b08645

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