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Altered Proteostasis in Neurodegenerative Tauopathies

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Proteostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1233))

Abstract

Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation or mutations of the neuronal microtubule-binding protein Tau. Tauopathies are characterized by accumulation of hyperphosphorylated Tau leading to formation of a range of aggregates including macromolecular ensembles such as Paired Helical filaments and Neurofibrilary Tangles whose morphology characterizes and differentiates these disease states. Why nonphysiological Tau proteins elude the surveillance normal proteostatic mechanisms and eventually form these macromolecular assemblies is a central mostly unresolved question of cardinal importance for diagnoses and potential therapeutic interventions. We discuss the response of the Ubiquitin–Proteasome system, autophagy and the Endoplasmic Reticulum-Unfolded Protein response in Tauopathy models and patients, revealing interactions of components of these systems with Tau, but also of the effects of pathological Tau on these systems which eventually lead to Tau aggregation and accumulation. These interactions point to potential disease biomarkers and future potential therapeutic targets.

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Acknowledgments

The authors acknowledge support for their research by:

KP: A grant from the Stavros Niarchos Foundation to the Biomedical Sciences Research Center “Alexander Fleming,” as part of the Foundation’s initiative to support the Greek research center ecosystem, Fondation Sante and ELIDEK.

EMCS: Fondation Sante and the project “Strategic Development of the Biomedical Research Institute ‘Alexander Fleming’” (MIS 5002562) which is implemented under the “Action for the Strategic Development on the Research and Technological Sector,” funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund).

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  1. Institute for Fundamental Biomedical Research, Biomedical Sciences Research Centre “Alexander Fleming”, Vari, Greece

    Katerina Papanikolopoulou & Efthimios M. C. Skoulakis

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  1. Katerina Papanikolopoulou
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  2. Efthimios M. C. Skoulakis
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Correspondence to Efthimios M. C. Skoulakis .

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  1. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    Rosa Barrio

  2. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    James D. Sutherland

  3. Centre Pierre Potier, ITAV, Toulouse Cedex 1, France

    Manuel S. Rodriguez

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Papanikolopoulou, K., Skoulakis, E.M.C. (2020). Altered Proteostasis in Neurodegenerative Tauopathies. In: Barrio, R., Sutherland, J., Rodriguez, M. (eds) Proteostasis and Disease . Advances in Experimental Medicine and Biology, vol 1233. Springer, Cham. https://doi.org/10.1007/978-3-030-38266-7_7

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