TAUCON and TAUCOM: A novel biosensor based on fluorescence resonance energy transfer for detecting tau hyperphosphorylation-associated cellular pathologies

Tauopathies are neurodegenerative diseases characterized by abnormal conformational changes in tau protein. Early hyperphosphorylation-induced conformational changes are considered a hallmark of tauopathy, but realtime tracking methods are lacking. Here, we present two novel fluorescence resonance energy transfer (FRET)based tau biosensors that detect such changes with high spatiotemporal resolution at the single-cell level. The TAUCON biosensor measures instantaneous conformational changes in hyperphosphorylated tau within 20 min, while the TAUCOM biosensor detects changes in the paper-clip structure of microtubule-associated tau. Our biosensors provide faster and more precise detection than conventional methods and can serve as valuable tools for investigating the initial causes, mechanisms, progression, and treatment of tauopathies.

Automated summary

The TAUCON and TAUCOM biosensors, based on fluorescence resonance energy transfer (FRET), can accurately detect abnormal conformational changes in tau protein at the single-cell level. These biosensors provide valuable tools for investigating the initial causes, mechanisms, progression, and treatment of tauopathies.