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Lost after translation: missorting of Tau protein and consequences for Alzheimer disease

Zempel, Hans, Mandelkow, Eckhard·2014·Trends in Neurosciences
DOI 10.1016/j.tins.2014.08.004
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Abstract

Tau is a microtubule-associated-protein that is sorted into neuronal axons in physiological conditions. In Alzheimer disease (AD) and other tauopathies, Tau sorting mechanisms fail and Tau becomes missorted into the somatodendritic compartment. In AD, aberrant amyloid-β (Aβ) production might trigger Tau missorting. The physiological axonal sorting of Tau depends on the developmental stage of the neuron, the phosphorylation state of Tau and the microtubule cytoskeleton. Disease-associated missorting of Tau is connected to increased phosphorylation and aggregation of Tau, and impaired microtubule interactions. Disease-causing mechanisms involve impaired transport, aberrant kinase activation, non-physiological interactions of Tau, and prion-like spreading. In this review we focus on the physiological and pathological (mis)sorting of Tau, the underlying mechanisms, and effects in disease.

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Cited by

Metadata

Authors
Zempel, H., & Mandelkow, E.
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2014-12
Volume
37
Issue
12
Pages
721-732
ISSN
0166-2236
DOI
10.1016/j.tins.2014.08.004
Cited by
265
References
34
Language
en
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)

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