Exploring Cimetidine as a Potential Therapeutic Attenuator against Amyloid Formation in Parkinson's Disease: Spectroscopic and Microscopic Insights into Alpha-Synuclein and Human Insulin.

Neurodegenerative diseases, notably Alzheimer's and Parkinson's, hallmark their progression through the formation of amyloid aggregates resulting from misfolding. While current therapeutics alleviate symptoms, they do not impede disease onset. In this context, repurposing existing drugs stands as a viable therapeutic strategy. Our study determines the antihistamine drug Cimetidine's potential as an inhibitor using diverse spectroscopic and microscopic methods on alpha-synuclein and human insulin amyloid formation, unveiling its efficacy. The thioflavin T (ThT) assay illustrated a dose-dependent reduction in amyloid formation with escalating concentrations of Cimetidine. Notably, the antihistamine drug maintained a helical structure and showed no significant conformational changes in the secondary structure. Confocal microscopy validated fewer fibrils in the Cimetidine-treated samples. Remarkably, Cimetidine interacted with pre-existing fibrils, leading to their disintegration. Further analyses (ThT, circular dichroism, and dynamic light scattering) showcased the conversion of fibrils into smaller aggregates upon Cimetidine addition. These findings signify the potential of this antihistamine drug as a plausible therapeutic option for Parkinson's disease. This study may open avenues for deeper investigations and possible therapeutic developments, emphasizing Cimetidine's promising role in mitigating neurodegenerative diseases like Parkinson's.