Mathematical modeling of reciprocal modulated reactions of the tau protein
Company 2013
EnVivo Pharmaceuticals, Watertown, USA
Hyperphosphorylation of tau protein is implicated in several neurodegenerative diseases. One of the approaches to tackle this process is to increase the levels of tau O-GlcNAcylation, as they are reciprocally regulated. Therefore, some therapeutical strategies are based on the inhibition of O-GlcNAcase. In this study, mathematical models are developed to analyse the dynamics of phosphorylation and O-GlcNAcylation of tau protein during O-GlcNAcase inhibition. The predictions show an increase of O-GlcNAcylated tau proportional to the inhibition levels and a non-dependent variable decrease of phosphorylated forms. This reduction in phosphorylated tau happens in short-term inhibitory scenarios and it is expected to return to its initial values under sustained inhibition, while O-GlcNAcylated proteins achieve higher steady levels. Furthermore, inhibition arrest is predicted to cause a temporal increase in phosphorylated tau levels. This model deciphers complex mechanisms in phosphorylation and O-GlcNAcylation co-regulation in different inhibitory strategies and can be a useful tool to design pharmacological interventions in scenarios where tau phosphorylation is a major pathological process.
A dynamic view to the modulation of phosphorylation and O-GlcNAcylation by inhibition of O-GlcNAcase
Cuyue Tang
Added on: 08-16-2021
[1] https://www.sciencedirect.com/science/article/abs/pii/S1476927113000200[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
