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Tau at the interface between neurodegeneration and neuroinflammation

Genes & Immunity volume 21, pages 288–300 (2020)Cite this article

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Abstract

Tau is an evolutionary conserved protein that promotes the assembly and stabilization of microtubules in neuronal axons. Complex patterns of posttranslational modifications (PTMs) dynamically regulate tau biochemical properties and consequently its functions. An imbalance in tau PTMs has been connected with a broad spectrum of neurodegenerative conditions which are collectively known as tauopathies and include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) among others. The hallmark of these neurological disorders is the presence in the brain of fibrillary tangles constituted of misfolded species of hyper-phosphorylated tau. The pathological events leading to tau aggregation are still largely unknown but increasing evidence suggests that neuroinflammation plays a critical role in tangle formation. Moreover, tau aggregation itself could enhance inflammation through feed-forward mechanisms, amplifying the initial neurotoxic insults. Protective effects of tau against neuroinflammation have been also documented, adding another layer of complexity to this phenomenon. Here, we will review the current knowledge on tau regulation and function in health and disease. In particular, we will address its emerging role in connecting neurodegenerative and neuroinflammatory processes.

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Fig. 1: Schematic representation of human MAPT genetic structure and tau protein isoforms.
Fig. 2: Alternative model for neuroinflammation in tau pathology.

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Acknowledgements

The author is grateful to Dr Jorge R. Oksenberg and Dr Carolina Alquezar Burillo for critically reading the paper. The work was supported by FISM-Fondazione Italiana Sclerosi Multipla Senior Research Fellowships Cod. 2014/B/1 and Cod. 2017/B/3 and financed or co-financed with the “5 per mille” public funding.

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    Alessandro Didonna

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Didonna, A. Tau at the interface between neurodegeneration and neuroinflammation. Genes Immun 21, 288–300 (2020). https://doi.org/10.1038/s41435-020-00113-5

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