Remodeling Tau and Prion Proteins Using Nanochaperons

There is increasing evidence that tau protein behaves in a prion-like manner in tauopathy. The stabilization of tau protein using a small molecular compound can limit tauopathy associated morbidity that advances with ageing. Here, a lab-on-a-chip experiment is reported, where gold citrate nanoparticles (5 nm, AuNPs) can remodel mutant tau protein (P301L) and prion, thus resolving the mutant tau- and prion-mediated impairment of kinesin cargo transport on microtubules. It is found that tau protein is overexpressed in Alzheimer's disease (AD) patient serum samples and the tau conformational change can also be affected in human serum samples of AD when treated with AuNPs ex vivo. Similarly, AuNPs reorganizing the prion protein and inducing conformational changes of prions in AD serum have been observed, while having no effect on alpha-synuclein in Parkinson patient serum. The mapping of AD serum mediated traffic jams, using particle tracking and mean square displacement analysis, and the observed recovery of uninterrupted processive motor functions by AuNP treatment show that kinesin cargo assays might be a useful method for future ex vivo validation of a targeted therapy against tauopathy before administration, a viable option to combat various neurodegenerative disorders arising from the susceptibility of amyloidogenic proteins toward aggregation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim