title: Mass Spectrometry Analysis of Lysine Posttranslational Modifications of Tau Protein from Alzheimer's Disease Brain.
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.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRBII Room 3M03, Baltimore, MD, 21218, USA. sthoma92@jhmi.edu.
authors.forename: Stefani N
authors.initials: SN
authors.lastname: Thomas
authors.affiliation: Department of Anatomy and Neurobiology, University of Maryland, Baltimore, MD, 21201, USA.|National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
authors.forename: Austin J
authors.initials: AJ
authors.lastname: Yang
mesh_terms: D000107:Acetylation; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011499:Protein Processing, Post-Translational; D053719:Tandem Mass Spectrometry; D054875:Ubiquitination; D016875:tau Proteins / Q000737:chemistry*
chemical_list: D016875:tau Proteins
keywords: Acetylation; Alzheimer’s disease (AD); Mass spectrometry; Methylation; Posttranslational modification; Tau; Ubiquitylation