Mass spectrometry analysis of lysine posttranslational modifications of Tau protein from Alzheimer’s disease brain

Stefani N. Thomas, Austin J. Yang

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

Recent advances in mass spectrometry (MS)-based proteomics have greatly facilitated the robust identification and quantification of posttranslational modifications (PTMs), including those that are present at substoichiometric site occupancies. The abnormal posttranslational modification and accumulation of the microtubule-associated protein tau has been implicated in the pathogenesis of Alzheimer’s disease (AD), and it is thought that the primary mode of regulation of tau occurs through PTMs. Several studies have been published regarding tau phosphorylation; however, other tau PTMs such as ubiquitylation, acetylation, methylation, oxidation, sumoylation, nitration, and glycosylation have not been analyzed as extensively. The comprehensive detection and delineation of these PTMs is critical for drug target discovery and validation. Lysine-directed PTMs including ubiquitylation, acetylation, and methylation play key regulatory roles with respect to the rates of tau turnover and aggregation. MS-based analytical approaches have been used to gain insight into the tau lysine-directed PTM signature that is most closely associated with neurofibrillary lesion formation. This chapter provides details pertaining to the liquid chromatography tandem mass spectrometry (LC-MS/MS)-based analysis of the lysine-directed posttranslational modification of tau.

Original languageEnglish (US)
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages161-177
Number of pages17
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Publication series

NameMethods in Molecular Biology
Volume1523
ISSN (Print)1064-3745

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Keywords

  • Acetylation
  • Alzheimer’s disease (AD)
  • Mass spectrometry
  • Methylation
  • Posttranslational modification
  • Tau
  • Ubiquitylation

Cite this

Thomas, S. N., & Yang, A. J. (2017). Mass spectrometry analysis of lysine posttranslational modifications of Tau protein from Alzheimer’s disease brain. In Methods in Molecular Biology (pp. 161-177). (Methods in Molecular Biology; Vol. 1523). Humana Press Inc.. https://doi.org/10.1007/978-1-4939-6598-4_10