What renders TAU toxic

Goetz, Juergen, Xia, Di, Leinenga, Gerhard, Chew, Yee Lian and Nicholas, Hannah R. (2013) What renders TAU toxic. Frontiers in Neurology, 4 72.1-72.10. doi:10.3389/fneur.2013.00072


Author Goetz, Juergen
Xia, Di
Leinenga, Gerhard
Chew, Yee Lian
Nicholas, Hannah R.
Title What renders TAU toxic
Journal name Frontiers in Neurology   Check publisher's open access policy
ISSN 1664-2295
Publication date 2013-06-10
Year available 2013
Sub-type Article (original research)
DOI 10.3389/fneur.2013.00072
Open Access Status DOI
Volume 4
Start page 72.1
End page 72.10
Total pages 10
Place of publication Lausanne, Switzerland
Publisher Frontiers Research Foundation
Collection year 2014
Language eng
Formatted abstract
TAU is a microtubule-associated protein that under pathological conditions such as Alzheimer's disease (AD) forms insoluble, filamentous aggregates. When 20 years after TAU's discovery the first TAU transgenic mouse models were established, one declared goal that was achieved was the modeling of authentic TAU aggregate formation in the form of neurofibrillary tangles. However, as we review here, it has become increasingly clear that TAU causes damage much before these filamentous aggregates develop. In fact, because TAU is a scaffolding protein, increased levels and an altered subcellular localization (due to an increased insolubility and impaired clearance) result in the interaction of TAU with cellular proteins with which it would otherwise either not interact or do so to a lesser degree, thereby impairing their physiological functions. We specifically discuss the non-axonal localization of TAU, the role phosphorylation has in TAU toxicity and how TAU impairs mitochondrial functions. A major emphasis is on what we have learned from the four available TAU knock-out models in mice, and the knock-out of the TAU/MAP2 homolog PTL-1 in worms. It has been proposed that in human pathological conditions such as AD, a rare toxic TAU species exists which needs to be specifically removed to abrogate TAU's toxicity and restore neuronal functions. However, what is toxic in one context may not be in another, and simply reducing, but not fully abolishing TAU levels may be sufficient to abrogate TAU toxicity.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 30 Jul 2013, 11:20:02 EST by Debra McMurtrie on behalf of Queensland Brain Institute