Summary
Posttranslational modifications such as phosphorylation and ubiquitination serve, independently or together, as gatekeepers of protein transport and turnover in normal and disease physiologies. Aberrant protein phosphorylation is one of the defining pathological hallmarks of more than 20 different neurodegenerative disorders, including Alzheimer’s disease (AD). The disruption of the phosphorylation of neurotransmitter receptors has been implicated as one of the causal factors of impaired memory function in AD (1–3). Another feature of AD is the aberrant accumulation of proteins that are normally degraded by the ubiquitin proteasome system upon being conjugated to ubiquitin. Thus, elucidating the protein targets of phosphorylation and ubiquitination that can serve as AD biomarkers will aid in the development of effective therapeutic approaches to the treatment of AD. This chapter provides details pertaining to the qualitative and quantitative liquid chromatography tandem mass spectrometry-based analysis of an affinity purified, phosphorylated, and ubiquitinated protein, paired-helical filament tau.
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Acknowledgments
The authors thank Peter Davies for providing the affinity-purified PHF-tau samples that we analyzed utilizing the methods detailed in this chapter. This work was supported by National Institutes of Health grants MH59786 and AG25323 (A.Y.).
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© 2009 Humana Press, a part of Springer Science+Business Media, LLC
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Thomas, S.N., Cripps, D., Yang, A.J. (2009). Proteomic Analysis of Protein Phosphorylation and Ubiquitination in Alzheimer’s Disease. In: Ottens, A., Wang, K. (eds) Neuroproteomics. Methods in Molecular Biology, vol 566. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-562-6_8
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DOI: https://doi.org/10.1007/978-1-59745-562-6_8
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