Remodeling Tau and Prion Proteins Using Nanochaperons.

Area of Science:

• Neuroscience
• Biochemistry
• Nanotechnology

Background:

• Tau protein exhibits prion-like behavior in tauopathies.
• Aging exacerbates tauopathy-related morbidity.
• Small molecules can stabilize tau protein to mitigate disease.

Purpose of the Study:

• To investigate the effect of gold citrate nanoparticles (AuNPs) on mutant tau protein and prions.
• To assess AuNP's ability to restore kinesin cargo transport impaired by tau and prions.
• To evaluate AuNPs' potential in diagnosing and treating tauopathies and other neurodegenerative diseases.

Main Methods:

• Lab-on-a-chip experiments utilizing 5 nm gold citrate nanoparticles (AuNPs).
• Analysis of kinesin cargo transport on microtubules using particle tracking and mean square displacement.
• Ex vivo treatment of Alzheimer's disease (AD) and Parkinson's disease patient serum samples with AuNPs.

Main Results:

• AuNPs remodeled mutant tau (P301L) and prions, resolving impaired kinesin transport.
• Tau protein overexpression and conformational changes in AD serum were modulated by AuNPs.
• AuNPs induced conformational changes in prions within AD serum but did not affect alpha-synuclein in Parkinson's serum.
• Kinesin cargo assays demonstrated recovery of motor function after AuNP treatment in AD serum.

Conclusions:

• AuNPs show promise in remodeling pathogenic tau and prion proteins.
• Kinesin cargo assays may serve as an ex vivo validation tool for targeted tauopathy therapies.
• AuNP treatment offers a potential strategy to combat neurodegenerative disorders linked to protein aggregation.