Posttranslational modifications of tau - Role in human tauopathies and modeling in transgenic animals

Chen F., David D., Ferrari A. and Gotz J. (2004) Posttranslational modifications of tau - Role in human tauopathies and modeling in transgenic animals. Current Drug Targets, 5 6: 503-515. doi:10.2174/1389450043345236


Author Chen F.
David D.
Ferrari A.
Gotz J.
Title Posttranslational modifications of tau - Role in human tauopathies and modeling in transgenic animals
Journal name Current Drug Targets   Check publisher's open access policy
ISSN 1389-4501
Publication date 2004
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/1389450043345236
Volume 5
Issue 6
Start page 503
End page 515
Total pages 13
Language eng
Subject 1313 Molecular Medicine
3003 Pharmaceutical Science
Abstract Alzheimer's disease (AD) is characterized histopathologically by β-amyloid-containing plaques, neurofibrillary tangles (NFT), reduced synaptic density, and neuronal loss in selected brain areas. Plaques consist of aggregates of a small peptide termed Aβ which is derived by proteolysis of the larger amyloid precursor protein APP, whereas NFT are composed of hyperphosphorylated forms of the microtubule-associated protein tau. Tau pathology in the presence of scant or no β-amyloid plaques characterizes additional neurodegenerative disorders collectively called tauopathies. In the course of plaque and NFT formation, the major proteinaceous components of these lesions undergo post-translational modifications. In the case of tau, these include phosphorylation of mainly serine and threonine, but also tyrosine residues. In addition, tau is subject to ubiquitination, nitration, truncation, prolyl isomerization, association with heparan sulfate proteoglycan, glycosylation, glycation and modification by advanced glycation end-products (AGEs). This review aims to provide insight into the complexity of tau modifications in human tauopathies such as AD and frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). Selected aspects of the post-translational modification of tau have been reproduced in transgenic animal models. Most of this work has been done in mice, but insight has also been gained from studies in the sea lamprey, the nematode C. elegans and Drosophila. Attempts have been made to link specific post-translational modifications with tau aggregation and nerve cell dysfunction.
Keyword Advanced glycation end products
Drosophila
Glycation
NFT
Phosphorylation
Tau
Transgenic mice
Truncation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
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Citation counts: TR Web of Science Citation Count  Cited 68 times in Thomson Reuters Web of Science Article | Citations
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