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Tau Assembly into Filaments

  • Mar Pérez
  • Raquel Cuadros
  • Miguel Medina
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1779)

Abstract

The brain-specific tau protein binds directly through microtubules to regulate dynamically its structure and function. It also plays a critical role in the pathogenesis of a number of neurodegenerative disorders collectively known as tauopathies, the most common of which is Alzheimer’s disease (AD). Under pathological conditions, the natively unfolded tau protein self-assembles into filamentous structures of aggregated, hyperphosphorylated tau. In AD brains, tau accumulates in the neuronal perikarya and processes as paired helical filaments (PHF) forming the neurofibrillary tangles (NFT) characteristic of the disease. Prominent tau neurofibrillary pathology is a common feature in all tauopathies and its development is associated with progressive neuronal loss and cognitive decline. A precise understanding of the cellular, biochemical, and structural mechanisms involved in the process of tau protein aggregation and fibril formation is key to design strategies to prevent, slow down, or stop the neurodegenerative pathway leading to neuronal loss in AD and other tauopathies. Herein, we describe some complementary experimental procedures for PHF purification from human postmortem brain, tau expression and purification, as well as in vitro formation of tau filaments from purified recombinant tau.

Key words

Aggregation Alzheimer’s disease Neurofibrillary tangles Paired helical filaments Tau Tauopathies 

Notes

Acknowledgments

We would like to thank Dr. Jesús Avila for helpful discussions throughout this work. This project was supported by the Carlos III Institute of Health and the Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-78603-R to MM).

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Anatomy, Histology and NeurosciencesUniversidad Autónoma de MadridMadridSpain
  2. 2.Centro de Biología Molecular “Severo Ochoa” CSIC-UAMMadridSpain
  3. 3.CIBERNED, Queen Sofia Foundation Alzheimer Center, CIEN FoundationInstituto de Salud Carlos IIIMadridSpain

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