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.