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.
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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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Pérez, M., Cuadros, R., Medina, M. (2018). Tau Assembly into Filaments. In: Sigurdsson, E., Calero, M., Gasset, M. (eds) Amyloid Proteins. Methods in Molecular Biology, vol 1779. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7816-8_27
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DOI: https://doi.org/10.1007/978-1-4939-7816-8_27
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