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Recent advances in cellular biosensor technology to investigate tau oligomerization

Tau is a microtubule binding protein which plays an important role in physiological functions but it is also involved in the pathogenesis of Alzheimer's disease and related tauopathies. While insoluble and β‐sheet containing tau neurofibrillary tangles have been the histopathological hallmark o...

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Autor principal: Lo, Chih Hung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459642/
https://www.ncbi.nlm.nih.gov/pubmed/34589603
http://dx.doi.org/10.1002/btm2.10231
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author Lo, Chih Hung
author_facet Lo, Chih Hung
author_sort Lo, Chih Hung
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description Tau is a microtubule binding protein which plays an important role in physiological functions but it is also involved in the pathogenesis of Alzheimer's disease and related tauopathies. While insoluble and β‐sheet containing tau neurofibrillary tangles have been the histopathological hallmark of these diseases, recent studies suggest that soluble tau oligomers, which are formed prior to fibrils, are the primary toxic species. Substantial efforts have been made to generate tau oligomers using purified recombinant protein strategies to study oligomer conformations as well as their toxicity. However, no specific toxic tau species has been identified to date, potentially due to the lack of cellular environment. Hence, there is a need for cell‐based models for direct monitoring of tau oligomerization and aggregation. This review will summarize the recent advances in the cellular biosensor technology, with a focus on fluorescence resonance energy transfer, bimolecular fluorescence complementation, and split luciferase complementation approaches, to monitor formation of tau oligomers and aggregates in living cells. We will discuss the applications of the cellular biosensors in examining the heterogeneous tau conformational ensembles and factors affecting tau self‐assembly, as well as detecting cell‐to‐cell propagation of tau pathology. We will also compare the advantages and limitations of each type of tau biosensors, and highlight their translational applications in biomarker development and therapeutic discovery.
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spelling pubmed-84596422021-09-28 Recent advances in cellular biosensor technology to investigate tau oligomerization Lo, Chih Hung Bioeng Transl Med Reviews Tau is a microtubule binding protein which plays an important role in physiological functions but it is also involved in the pathogenesis of Alzheimer's disease and related tauopathies. While insoluble and β‐sheet containing tau neurofibrillary tangles have been the histopathological hallmark of these diseases, recent studies suggest that soluble tau oligomers, which are formed prior to fibrils, are the primary toxic species. Substantial efforts have been made to generate tau oligomers using purified recombinant protein strategies to study oligomer conformations as well as their toxicity. However, no specific toxic tau species has been identified to date, potentially due to the lack of cellular environment. Hence, there is a need for cell‐based models for direct monitoring of tau oligomerization and aggregation. This review will summarize the recent advances in the cellular biosensor technology, with a focus on fluorescence resonance energy transfer, bimolecular fluorescence complementation, and split luciferase complementation approaches, to monitor formation of tau oligomers and aggregates in living cells. We will discuss the applications of the cellular biosensors in examining the heterogeneous tau conformational ensembles and factors affecting tau self‐assembly, as well as detecting cell‐to‐cell propagation of tau pathology. We will also compare the advantages and limitations of each type of tau biosensors, and highlight their translational applications in biomarker development and therapeutic discovery. John Wiley & Sons, Inc. 2021-06-01 /pmc/articles/PMC8459642/ /pubmed/34589603 http://dx.doi.org/10.1002/btm2.10231 Text en © 2021 The Author. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Lo, Chih Hung
Recent advances in cellular biosensor technology to investigate tau oligomerization
title Recent advances in cellular biosensor technology to investigate tau oligomerization
title_full Recent advances in cellular biosensor technology to investigate tau oligomerization
title_fullStr Recent advances in cellular biosensor technology to investigate tau oligomerization
title_full_unstemmed Recent advances in cellular biosensor technology to investigate tau oligomerization
title_short Recent advances in cellular biosensor technology to investigate tau oligomerization
title_sort recent advances in cellular biosensor technology to investigate tau oligomerization
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459642/
https://www.ncbi.nlm.nih.gov/pubmed/34589603
http://dx.doi.org/10.1002/btm2.10231
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