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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023. The Author(s).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.
Author(s): Rosado-Ramos R, Pocas GM, Marques D, Foito A, Sevillano DM, Lopes-da-Silva M, Goncalves LG, Menezes R, Ottens M, Stewart D, Ibanez de Opakua A, Zweckstetter M, Seabra MC, Mendes CS, Outeiro TF, Domingos PM, Santos CN
Publication type: Article
Publication status: Published
Journal: Nature Communications
Online publication date: 06/04/2023
Acceptance date: 20/03/2023
Date deposited: 02/05/2023
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
PubMed id: 37024503
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