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Tau Biology pp 359–372Cite as

The Pathophysiology of Tau and Stress Granules in Disease

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1184))

Abstract

This chapter discusses the relationship between tau, RNA binding proteins and stress granules, which exhibit an intimate bidirectional relationship affecting the functions of both tau and the translational stress response. We describe how tau becomes hyperphosphorylated and oligomerized as part of an endogenous mechanism to promote the translational stress response through interaction with RNA binding proteins. Prior studies demonstrate that dysfunction of RNA binding proteins biology is sufficient to cause neurodegenerative diseases, such as amyotrophic lateral sclerosis and frontotemporal dementia. Emerging evidence indicates that tau-mediated neurodegeneration also occurs through a mechanism that is mediated by RNA binding proteins and the translational stress response. Discovery of the role of RNA metabolism in tauopathy opens a wide variety of novel therapeutic approaches. Multiple studies have already shown that approaches reducing the levels of selected RNA binding proteins or inhibiting the translational stress response can intervene in the pathophysiology of motoneuron diseases. Emerging studies show that reducing the levels of selected RNA binding proteins or inhibiting the translational stress response also reduces neurodegeneration in models of tauopathy and Aβ mediated degeneration. The combined impact of these studies indicate that RNA binding proteins and RNA metabolism represent a valuable new frontier for the investigation and treatment tauopathies.

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Acknowledgements

This work was supported by funding to BW from the NIH (AG050471, NS089544, AG056318), BrightFocus Foundation, Alzheimer Association, Cure Alzheimer’s Fund and the Thome Medical Foundation.

Conflict of Interest

BW is co-founder and Chief Scientific Officer of Aquinnah Pharmaceuticals Inc., www.aquinnahpharma.com.

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Author notes

  1. Authors Anna Cruz and Mamta Verma have been equally contributed to this chapter.

Authors and Affiliations

  1. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Anna Cruz, Mamta Verma & Benjamin Wolozin

  2. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. Program in Neuroscience, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

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  1. Anna Cruz
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Correspondence to Benjamin Wolozin .

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  1. Department of Life Sciences, Gakushuin University, Tokyo, Japan

    Akihiko Takashima

  2. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. University of Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Luc Buee

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Cruz, A., Verma, M., Wolozin, B. (2019). The Pathophysiology of Tau and Stress Granules in Disease. In: Takashima, A., Wolozin, B., Buee, L. (eds) Tau Biology. Advances in Experimental Medicine and Biology, vol 1184. Springer, Singapore. https://doi.org/10.1007/978-981-32-9358-8_26

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