Targeting Lysozyme-Linked Amyloidosis through Piperine-Functionalized Gold Nanoparticles

Area of Science:

• Biochemistry
• Materials Science
• Nanotechnology

Background:

• Misfolded human lysozyme (HuL) accumulation causes non-neuropathic systemic amyloidosis.
• Amyloid deposits feature cross β-sheet conformers and polymorphic fibrils, complicating therapeutic design.
• Targeting aggregation-prone regions in HuL is crucial for developing effective anti-amyloid interventions.

Purpose of the Study:

• To design an antiamyloid metal nanoparticle formulation targeting exposed hydrophobic stretches in HuL.
• To synthesize and characterize piperine-coated gold nanoparticles (AuNPs^Pip) for amyloid inhibition.
• To investigate the efficacy of AuNPs^Pip in preventing and disassembling HuL amyloid aggregates.

Main Methods:

• Synthesis and characterization of piperine-coated gold nanoparticles (AuNPs^Pip).
• Thioflavin T (ThT) fluorescence assays to monitor HuL aggregation.
• Dynamic light scattering (DLS) and fluorescence microscopy to confirm aggregation inhibition.
• Studies on the interaction of AuNPs^Pip with preformed amyloid fibrils and seed-induced aggregation.

Main Results:

• AuNPs^Pip significantly inhibited HuL aggregation, confirmed by ThT assays, DLS, and microscopy.
• AuNPs^Pip prevented seed-induced aggregation and disassembled preformed amyloid fibrils.
• Neither bare gold nanoparticles (AuNPs) nor piperine alone showed significant anti-amyloid activity.
• Experimental and computational analyses indicated that AuNPs^Pip maintain HuL native structure and interact with aggregation-prone residues.

Conclusions:

• Piperine-coated gold nanoparticles represent a novel and effective strategy against human lysozyme amyloidosis.
• AuNPs^Pip demonstrate dual action: inhibiting initial aggregation and disassembling existing fibrils.
• This nanoparticle formulation holds potential for developing therapeutics for pathologies linked to lysozyme aggregation.