Studies of structure and phosphorylation of tau protein using high resolution mass spectrometry

Abstract

Tau as a microtubule-associated protein (MAP) is involved in promoting microtubule assembly and stabilizing the microtubulus in vivo and has recently gained widespread interest as a target protein in neurofibrillary tangles characteristic of Alzheimer’s disease and other neurodegenerative disorders. One important part in analysing the tau protein and its isoforms is the study of the dephosphorylation reactions by using different phosphatases. In this work alkaline phosphatase and λ-phosphatase were used for the dephosphorylation of tau protein isoforms. The different isoforms of tau were separated after the reactions by 1D gel electrophoresis. For the analysis of the phosphorylation sites MALDI-FTICR-MS was used after tryptic digestion. The pathophysiological aggregation of tau in fibrillary tangles of brain tissue has been shown to be associated with structural changes by multi- or hyperphosphorylation.