Modulation of aggregation with an electric field; scientific roadmap for a potential non-invasive therapy against tauopathies

Abstract

Toxic aggregation of tau protein to neurofibrillary tangles (NFTS) is a central pathological event involved in tauopathies. Inhibition of tau protein aggregation can serve as a straightforward therapeutic strategy. However, tau-based therapeutic solutions are not very common. Phenothiazine methylene blue (tau protein inhibitor) is currently the only drug under phase III clinical trials. In this work, a non-invasive strategy is presented for modulating the aggregation of core peptide segments of tau protein (VQIVYK and VQIINK) by using electric fields of varying strengths. We use thioflavin T staining, tyrosine fluorescence assay, electron microscopy, IR, dynamic and static light scattering, and neuronal toxicity estimation, for verifying the effect of electric field on the aggregation kinetics, morphology, conformational state and cellular toxicity of peptide systems. Our observations suggest that electric field arrests the self-assembly of VQIVYK and VQIINK fibrils thereby reducing the neurotoxicity instigated by them. Based on our observations, we propose a prospective scheme for a futuristic non-invasive therapeutic device.