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Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

© 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.

Publication metadata

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

Year: 2023

Volume: 14

Issue: 1

Online publication date: 06/04/2023

Acceptance date: 20/03/2023

Date deposited: 02/05/2023

ISSN (electronic): 2041-1723

Publisher: Nature Publishing Group

URL: https://doi.org/10.1038/s41467-023-37561-2

DOI: 10.1038/s41467-023-37561-2

PubMed id: 37024503

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