Potential effect of nanoformulated iota carrageenan in Aβ1-42 disaggregation: an in vitro, in vivo and in silico study.
BACKGROUND AND PURPOSE: Alzheimer's disease is the primary contributor to neurodegenerative conditions. These pathologies are identified by the deposition of β-amyloid peptide within brain regions. It develops insoluble fibrils known as senile plaques. These plaques are associated with synaptic dysfunction, neuroinflammation, and progressive cognitive decline. Hence, the degradation and elimination of β-amyloid peptide fibrils from the body are viable therapeutic approaches for managing Alzheimer's disease. EXPERIMENTAL APPROACH: In the current study, liposomal nanoformulated iota carrageenan was synthesized and characterized using different photophysical tools. The nanoformulated iota carrageenan effectively degraded β-amyloid peptide 1-42, with 45.5 % reduction confirmed by Thioflavin T fluorescence assay. This activity was further supported by turbidity and dynamic light scattering analysis. KEY RESULTS: The biocompatibility of nanoformulated iota carrageenan and its degraded β-amyloid peptide was determined using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), live/dead cell assay on PC12 cells. Structural disintegration of the β-amyloid peptide fibrils was validated through atomic force microscopy, revealing a significant reduction in fibrillar morphology. In silico studies also evidenced the interaction between the β-amyloid peptide and nanoformulated iota carrageenan. In addition, the neuroprotective potential of nanoformulated iota carrageenan, as evidenced by nanoformulated iota carrageenan-treated β-amyloid peptide, was supported by neurite outgrowth studies. These studies showed that differentiated PC12 cells exhibited larger neurite growth with extensive branching, indicating the reversal of β-amyloid peptide-induced neurotoxicity. CAM assay demonstrated enhanced blood vessel formation in chick embryos treated with nanoformulated iota carrageenan and its β-amyloid peptide-degraded group. CONCLUSION: These findings suggest that nanoformulated iota carrageenan holds potential and has nontoxic therapeutic effects for Alzheimer's disease. Additional in vivo validation is required in future investigations.