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Open Access 01-12-2015 | Research

Posttranslational modifications of α-tubulin in alzheimer disease

Authors: Fan Zhang, Bo Su, Chunyu Wang, Sandra L. Siedlak, Siddhartha Mondragon-Rodriguez, Hyoung-gon Lee, Xinglong Wang, George Perry, Xiongwei Zhu

Published in: Translational Neurodegeneration | Issue 1/2015

Abstract

Background

In Alzheimer disease (AD), hyperphosphorylation of tau proteins results in microtubule destabilization and cytoskeletal abnormalities. Our prior ultra-morphometric studies documented a clear reduction in microtubules in pyramidal neurons in AD compared to controls, however, this reduction did not coincide with the presence of paired helical filaments. The latter suggests the presence of compensatory mechanism(s) that stabilize microtubule dynamics despite the loss of tau binding and stabilization. Microtubules are composed of tubulin dimers which are subject to posttranslational modifications that affect the stability and function of microtubules.

Methods

In this study, we performed a detailed analysis on changes in the posttranslational modifications in tubulin in postmortem human brain tissues from AD patients and age-matched controls by immunoblot and immunocytochemistry.

Results

Consistent with our previous study, we found decreased levels of α-tubulin in AD brain. Levels of tubulin with various posttranslational modifications such as polyglutamylation, tyrosination, and detyrosination were also proportionally reduced in AD brain, but, interestingly, there was an increase in the proportion of the acetylated α-tubulin in the remaining α-tubulin. Tubulin distribution was changed from predominantly in the processes to be more accumulated in the cell body. The number of processes containing polyglutamylated tubulin was well preserved in AD neurons. While there was a cell autonomous detrimental effect of NFTs on tubulin, this is likely a gradual and slow process, and there was no selective loss of acetylated or polyglutamylated tubulin in NFT-bearing neurons.

Conclusions

Overall, we suggest that the specific changes in tubulin modification in AD brain likely represent a compensatory response.

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Title: Posttranslational modifications of α-tubulin in alzheimer disease
Authors: Fan Zhang
Bo Su
Chunyu Wang
Sandra L. Siedlak
Siddhartha Mondragon-Rodriguez
Hyoung-gon Lee
Xinglong Wang
George Perry
Xiongwei Zhu
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Translational Neurodegeneration / Issue 1/2015
Electronic ISSN: 2047-9158
DOI: https://doi.org/10.1186/s40035-015-0030-4

2024 ASCO Annual Meeting

Springer Medicine

Posttranslational modifications of α-tubulin in alzheimer disease

Abstract

Background

Methods

Results

Conclusions

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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