EFFECT OF AMAZONIAN Banisteriopsis caapi EXTRACT ON THE DISAGGREGATION OF THE AMYLOIDOGENIC PROTEIN α-SYNUCLEIN INVOLVED IN PARKINSON´S DISEASE

INTRODUCTION: The accumulation of protein aggregates is a hallmark of several neurodegenerative diseases, including Parkinson’s Disease (PD), where intracellular inclusions of α-Synuclein (aSyn), known as Lewy bodies, are key pathological features. As no curative treatment exists, aSyn aggregates are a promising therapeutic target. Small molecules that inhibit fibril formation and promote disaggregation of β-sheet-rich structures are strong candidates for disease-modifying therapies. Inspired by Brazil’s biodiversity, we investigated the effects of Banisteriopsis caapi (B. caapi), a plant endemic to the Amazon and traditionally used in religious rituals, on aSyn aggregation. OBJECTIVE: To evaluate the disaggregation potential of B. caapi extract and its major alkaloids, Harmine (HMN) and Harmaline (HML), on aSyn aggregates. METHODS: Recombinant aSyn was expressed in E. coli and purified. Disaggregation was assessed by ThT fluorescence in the presence of B. caapi extract, HMN, or HML. Endpoints were analyzed using Transmission Electron Microscopy (TEM), Circular Dichroism (CD), and Light Scattering. Effects on intracellular aggregation were tested using H4 neuroglioma cells expressing aSyn, and inclusions were quantified with and without treatment. RESULTS AND DISCUSSION: Our results show that B. caapi extract (0.1–1 mg/mL) and the alkaloids HMN and HML (70–700 µM) effectively disaggregate amyloid fibers, significantly reducing their abundance in vitro experiments. They also influence intracellular models by reducing aSyn deposits within cells. CONCLUSION: These findings suggest that B. caapi extract and its major alkaloids are promising candidates for disaggregating and remodeling aSyn aggregates and hold potential for the development of novel therapeutic strategies for Parkinson’s Disease.