Tryptophan-cardanol fluorescent nanoparticles inhibit α-synuclein aggregation and disrupt amyloid fibrils.

Protein misfolding and aggregation play a vital role in several human diseases such as Parkinson's, Alzheimer's, and prion diseases. The development of nanoparticles that modulate aggregation could be potential drug candidates for these neurodegenerative disorders. Parkinson's disease pathogenesis is closely associated with the accumulation of α-synuclein oligomers and fibrils in the substantia nigra of the brain. This report discusses the interactions of novel tryptophan-cardanol nanoparticles with α-synuclein protein monomers and fibrils. These nanoparticles could effectively disrupt α-synuclein fibrils and inhibit fibril formation at low concentrations such as 5 μM. The tryptophan-cardanol nanoparticles inhibit fibril formation from unstructured protein resulting in spherical nanostructures. These nanoparticles could also disassemble amyloid fibrils; the complete disappearance of fibrils was evident after 48 h of incubation with tryptophan-cardanol. The transmission electron microscopy (TEM) micrographs after the incubation did not show any remnants of the peptide aggregates or oligomers. The thioflavin T fluorescence after the disassembly was diminished compared with that of fibrils also supports the inhibitory effect of the nanoparticles. Also, these nanoparticles did not reduce the viability of the SH-SY5Y cells. These findings suggest that the tryptophan-cardanol nanoparticles showed sufficiently high inhibitory activity and may have therapeutic potential for synucleinopathies.