The Many Faces of Tau

Morris, Meaghan; Maeda, Sumihiro; Vossel, Keith A.; Mucke, Lennart

doi:10.1016/j.neuron.2011.04.009

Cited by 769 publications

(741 citation statements)

References 195 publications

(309 reference statements)

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“…Immunotherapy has been shown to clear tau aggregates from transgenic mouse brain and to reduce functional impairment (Asuni et al 2007). Because aggregation is a concentrationdependent process, a reduction in production and/or increased clearance of tau are also potential targets (Morris et al 2011).…”

Section: Implications For Understanding Alzheimer Diseasementioning

confidence: 99%

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

Goedert¹,

Ghetti²,

Spillantini³

2011

Cold Spring Harbor Perspectives in Medicine

138

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Section: Implications For Understanding Alzheimer Diseasementioning

confidence: 99%

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

Goedert¹,

Ghetti²,

Spillantini³

2011

Cold Spring Harbor Perspectives in Medicine

138

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“…These observations established a role for Tau in its own right as a disease-causing agent. Why Tau and Ab enter a special relationship in AD is still a matter of debate, but recent results from transgenic mice suggest that Tau pathology is not simply a downstream consequence of Ab pathology, but necessary for the appearance of Ab-induced toxicity (for a review, see Morris et al 2011).…”

mentioning

confidence: 99%

“…A number of excellent reviews on the biology and pathology of Tau have appeared over the past few years (Cassimeris and Spittle 2001;Garcia and Cleveland 2001;Terwel et al 2002;Dehmelt and Halpain 2005;Andreadis 2006;Ballatore et al 2007;Gotz et al 2007Gotz et al , 2010Schneider and Mandelkow 2008;Sergeant et al 2008;Aguzzi and Rajendran 2009;Spires-Jones et al 2009;Iqbal et al 2009;Wolfe 2009;Goedert et al 2010;Morris et al 2011;Salminen et al 2011). This brief review will cover a few salient aspects, with an emphasis on Tau structure and interactions.…”

mentioning

confidence: 99%

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration

Mandelkow

2012

Cold Spring Harbor Perspectives in Medicine

705

636

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Tau represents the subunit protein of one of the major hallmarks of Alzheimer disease (AD), the neurofibrillary tangles, and is therefore of major interest as an indicator of disease mechanisms. Many of the unusual properties of Tau can be explained by its nature as a natively unfolded protein. Examples are the large number of structural conformations and biochemical modifications ( phosphorylation, proteolysis, glycosylation, and others), the multitude of interaction partners (mainly microtubules, but also other cytoskeletal proteins, kinases, and phosphatases, motor proteins, chaperones, and membrane proteins). The pathological aggregation of Tau is counterintuitive, given its high solubility, but can be rationalized by short hydrophobic motifs forming b structures. The aggregation of Tau is toxic in cell and animal models, but can be reversed by suppressing expression or by aggregation inhibitors. This review summarizes some of the structural, biochemical, and cell biological properties of Tau and Tau fibers. Further aspects of Tau as a diagnostic marker and therapeutic target, its involvement in other Tau-based diseases, and its histopathology are covered by other chapters in this volume.

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“…3 In AD and other tauopathies, tau becomes hyperphosphoryled, which destabilizes the microtubule binding, resulting in tau aggregation. 3 The tau pathology occurs in the later stage of disease progression. 4 Aβ toxicity can be prevented by tau reduction or deficiency as evidenced by transgenic mouse studies.…”

mentioning

confidence: 99%

Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via the Fyn Pathway

Chen

Chang

Lin

et al. 2013

ACS Chem. Neurosci.

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Amyloid-β (Aβ) and tau are the pathogenic hallmarks in Alzheimer's disease (AD). Aβ oligomers are considered the actual toxic entities, and the toxicity relies on the presence of tau. Recently, Aβ oligomers have been shown to specifically interact with cellular prion protein (PrP C ) where the role of PrP C in AD is still not fully understood. To investigate the downstream mechanism of PrP C and Aβ oligomer interaction and their possible relationships to tau, we examined tau expression in human neuroblastoma BE(2)-C cells transfected with murine PrP C and studied the effect under Aβ oligomer treatment. By Western blotting, we found that PrP C overexpression down-regulated tau protein and Aβ oligomer binding alleviated the tau reduction induced by wild type but not M128V PrP C , the high AD risk polymorphic allele in human prion gene. PrP C lacking the Aβ oligomer binding site was incapable of rescuing the level of tau reduction. Quantitative RT-PCR showed the PrP C effect was attributed to tau reduction at the transcription level. Treatment with Fyn pathway inhibitors, Fyn kinase inhibitor PP2 and MEK inhibitor U0126, reversed the PrP C -induced tau reduction and Aβ oligomer treatment modulated Fyn kinase activity. The results suggested Fyn pathway regulated Aβ−PrP C −tau signaling. Overall, our results demonstrated that PrP C down-regulated tau via the Fyn pathway and the effect can be regulated by Aβ oligomers. Our study facilitated the understanding of molecular mechanisms among PrP C , tau, and Aβ oligomers.

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The Many Faces of Tau

Cited by 769 publications

References 195 publications

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

Frontotemporal Dementia: Implications for Understanding Alzheimer Disease

Biochemistry and Cell Biology of Tau Protein in Neurofibrillary Degeneration

Alzheimer’s Amyloid-β Oligomers Rescue Cellular Prion Protein Induced Tau Reduction via the Fyn Pathway

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