Blocking tau transmission by biomimetic graphene nanoparticles

Abstract

Tauopathies are a class of neurodegenerative diseases resulting in cognitive dysfunction, executive dysfunction, and motor disturbance. The primary pathological feature of tauopathies is the presence of neurofibrillary tangles in the brain composed of tau protein aggregates. Moreover, tau aggregates can spread from neuron to neuron and lead to the propagation of tau pathology. Although numerous small molecules are known to inhibit tau aggregation and block tau cell-to-cell transmission, it is still challenging to use them for therapeutic applications due to poor specificity and low blood-brain barrier (BBB) penetration. Graphene nanoparticles were previously demonstrated to penetrate the BBB and are amenable to functionalization for targeted delivery. Moreover, these nanoscale biomimetic particles can self-assemble or assemble with various biomolecules including proteins. In this paper, we show that graphene quantum dots (GQDs), as graphene nanoparticles, block the seeding activity of tau fibrils by inhibiting the fibrillization of monomeric tau and triggering the disaggregation of tau filaments. This behavior is attributed to electrostatic and π–π stacking interactions of GQDs with tau. Overall, our studies indicate that GQDs with biomimetic properties can efficiently inhibit and disassemble pathological tau aggregates, and thus block tau transmission, which supports their future developments as a potential treatment for tauopathies.