Exploring Cimetidine\nas a Potential Therapeutic Attenuator\nagainst Amyloid Formation in Parkinson’s Disease: Spectroscopic\nand Microscopic Insights into Alpha-Synuclein and Human Insulin

Neurodegenerative diseases, notably Alzheimer’s\nand Parkinson’s,\nhallmark their progression through the formation of amyloid aggregates\nresulting from misfolding. While current therapeutics alleviate symptoms,\nthey do not impede disease onset. In this context, repurposing existing\ndrugs stands as a viable therapeutic strategy. Our study determines\nthe antihistamine drug Cimetidine’s potential as an inhibitor\nusing diverse spectroscopic and microscopic methods on alpha-synuclein\nand human insulin amyloid formation, unveiling its efficacy. The thioflavin\nT (ThT) assay illustrated a dose-dependent reduction in amyloid formation\nwith escalating concentrations of Cimetidine. Notably, the antihistamine\ndrug maintained a helical structure and showed no significant conformational\nchanges in the secondary structure. Confocal microscopy validated\nfewer fibrils in the Cimetidine-treated samples. Remarkably, Cimetidine\ninteracted with pre-existing fibrils, leading to their disintegration.\nFurther analyses (ThT, circular dichroism, and dynamic light scattering)\nshowcased the conversion of fibrils into smaller aggregates upon Cimetidine\naddition. These findings signify the potential of this antihistamine\ndrug as a plausible therapeutic option for Parkinson’s disease.\nThis study may open avenues for deeper investigations and possible\ntherapeutic developments, emphasizing Cimetidine’s promising\nrole in mitigating neurodegenerative diseases like Parkinson’s.