Hexagonal Boron Nitride Nanoparticles for Inhibition of Small Fragment Tau Aggregation

Area of Science:

• Biophysics
• Materials Science
• Neuroscience

Background:

• Aberrant Tau protein folding is linked to neurodegenerative diseases such as Alzheimer's and tauopathies.
• Specific Tau fragments, PHF6 and PHF6*, are key drivers of Tau aggregation and represent therapeutic targets.
• Low-dimensional nanomaterials show promise in treating amyloid diseases due to their biocompatibility and low cytotoxicity.

Purpose of the Study:

• To investigate the aggregation patterns of PHF6 and PHF6* peptides.
• To explore the impact of two-dimensional hexagonal boron nitride nanosheets (BNNS) on Tau peptide oligomerization.
• To evaluate BNNS as a potential anti-amyloid therapeutic agent.

Main Methods:

• Atomistic simulations were employed to model peptide aggregation and interactions.
• The study analyzed the effects of BNNS on PHF6 and PHF6* monomeric and oligomeric states.
• Interactions between peptides and the BNNS surface were examined.

Main Results:

• PHF6 homomer aggregation is favored by aromatic π-π interactions, and PHF6-PHF6* heteromeric interactions are stronger than PHF6* self-association.
• BNNS adsorbs peptides via hydrophobic interactions and π-π stacking, maintaining their random coil structure.
• BNNS effectively destabilizes pre-formed hexapeptide oligomers.

Conclusions:

• Hexagonal boron nitride nanosheets inhibit Tau peptide aggregation by preventing oligomer formation.
• BNNS demonstrates potential as an anti-amyloid agent for treating tauopathies.
• This research opens new avenues for utilizing hexagonal boron nitride in nanomedicine for neurodegenerative disease treatment.