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Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage
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Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage
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Journal Article
Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage
2023
Overview
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.
In this work, the authors identify Genipin as a small iridoid able to prevent alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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/ 14/19
/ 14/28
/ 14/34
/ 14/35
/ 14/63
/ 140/131
/ 38
/ 38/77
/ 38/91
/ 42
/ 45
/ 64/24
/ 82/16
/ 82/58
/ alpha-Synuclein - metabolism
/ Animals
/ Drosophila melanogaster - metabolism
/ Genetics and Molecular Biology(all)
/ Genipin
/ Humanities and Social Sciences
/ Lipids
/ Parkinson Disease - metabolism
/ Phenols
/ Science
/ Toxicity
