Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage
Rita Rosado-Ramos (Universidade Nova de Lisboa, Instituto de Biologia Experimental e Tecnológica)
Gonçalo M. Poças (Universidade Nova de Lisboa)
Daniela Marques (Universidade Nova de Lisboa)
Alexandre Foito (The James Hutton Institute)
David M Sevillano (Student TU Delft)
Mafalda Lopes-da-Silva (Universidade Nova de Lisboa)
Luís G. Gonçalves (Universidade Nova de Lisboa)
Regina Menezes (Instituto de Biologia Experimental e Tecnológica, Universidade Lusófona’s Research Center for Biosciences & Health Technologies, Lisboa, Universidade Nova de Lisboa)
Marcel Ottens (TU Delft - Applied Sciences)
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Abstract
Parkinson's Disease (PD) is a common neurodegenerative disorder affecting millions of people worldwide for which there are only symptomatic therapies. Small molecules able to target key pathological processes in PD have emerged as interesting options for modifying disease progression. We have previously shown that a (poly)phenol-enriched fraction (PEF) of Corema album L. leaf extract modulates central events in PD pathogenesis, namely α-synuclein (αSyn) toxicity, aggregation and clearance. PEF was now subjected to a bio-guided fractionation with the aim of identifying the critical bioactive compound. We identified genipin, an iridoid, which relieves αSyn toxicity and aggregation. Furthermore, genipin promotes metabolic alterations and modulates lipid storage and endocytosis. Importantly, genipin was able to prevent the motor deficits caused by the overexpression of αSyn in a Drosophila melanogaster model of PD. These findings widens the possibility for the exploitation of genipin for PD therapeutics.
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