Electrochemical modulation of tau protein phosphorylation levels with biomimetic polyaniline membranes

Alzheimer's disease (AD) is hallmarked by the accumulation of hyperphosphorylated tau proteins, which disrupt microtubule stability and significantly contribute to neurodegeneration and cognitive decline. Despite existing therapies targeting tau pathologies, their efficacy remains limited, underscoring the urgent need for innovative therapeutic approaches. A novel electrochemical method utilizing conductive polyaniline (PANI) membranes to effectively regulate tau protein phosphorylation levels was investigated. Reversing tau hyperphosphorylation provides a groundbreaking therapeutic strategy for AD, opening new avenues for more effective treatment modalities and improving patient outcomes. The research demonstrates that phosphorylated tau peptides and proteins adhere effectively to PANI membranes under electrostatic stimulation. The results of AFM analysis revealed variation in surface morphology between the bare electrode and the tau protein/PANI-modified electrode, indicating that PANI forms an even, smooth membrane that attracts p-tau through positive potential rather than protein self-aggregation. Optimal adsorption potentials were identified at 0.5 V for pS214 peptides and 0.3 V for phosphorylated tau proteins. Electrochemical quartz crystal microbalance (EQCM) measurements showcased a maximum adsorption efficiency of 40 %, with desorption efficiencies reaching 16.67 % at negative potentials. Furthermore, alternating positive and negative potentials enabled repeated and precise control over tau attachment and detachment from the PANI membranes. This dynamic regulation was verified through mass spectrometry, which confirmed the removal of phosphate groups during the process. The proposed electrochemical approach offers a precise method for controlling phosphate group concentrations in tau peptides and proteins. This precision supports the development of biocompatible implants that could be instrumental in treating neurodegenerative diseases.