Targeting protein aggregation using a cocoa-bean shell extract to reduce α-synuclein toxicity in models of Parkinson's disease

Abstract

Neurodegenerative diseases are among the major challenges in modern medicine, due to the progressive aging of the world population. Among these, Parkinson's disease (PD) affects 10 million people worldwide and is associated with the aggregation of the presynaptic protein α-synuclein (α-syn). Here we use two different PD models, yeast cells and neuroblastoma cells overexpressing α-syn, to investigate the protective effect of an extract from the cocoa shell, which is a by-product of the roasting process of cocoa beans. The LC-ESI-qTOF-MS and NMR analyses allow the identification of amino acids (including the essential ones), organic acids, lactate and glycerol, confirming also the presence of the two methylxanthines, namely caffeine and theobromine. The present study demonstrates that the supplementation with the cocoa bean shell extract (CBSE) strongly improves the longevity of yeast cells expressing α-syn, reducing the level of reactive oxygen species, activating autophagy and reducing the intracellular protein aggresomes. These anti-aggregation properties are confirmed also in neuroblastoma cells, where CBSE treatment leads to activation of AMPK kinase and to a significant reduction of toxic α-syn oligomers. Results obtained by surface plasmon resonance (SPR) assay highlights that CBSE binds α-syn protein in a concentration-dependent manner, supporting its inhibitory role on the amyloid aggregation of α-syn. These findings suggest that the supplementation with CBSE in the form of nutraceuticals may represent a promising way to prevent neurodegenerative diseases associated with α-syn aggregation.

Keywords

• Saccharomyces cerevisiae
• Human α-synuclein
• Parkinson's disease (PD)
• Cocoa
• Food waste valorization