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

Rita Rosado-Ramos, Gonçalo M. Poças, Daniela Marques, Alexandre Foito, David M Sevillano, Mafalda Lopes-da-Silva, Luís G. Gonçalves, Regina Menezes, Marcel Ottens, Derek Stewart, Alain Ibáñez de Opakua, Markus Zweckstetter, Miguel C. Seabra, César S. Mendes, Tiago Fleming Outeiro, Pedro M. Domingos, Cláudia N. Santos

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)
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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.

Original languageEnglish
Article number1918
Pages (from-to)1918
Number of pages1
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 6 Apr 2023

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