REVIEW article
Front. Mol. Neurosci.
Sec. Molecular Signalling and Pathways
This article is part of the Research TopicPhysiopathology of alpha-synuclein: a bench-to-bedside overviewView all 5 articles
Interplay between lipid droplets and Alpha-Synuclein: Implication in Parkinson's disease pathogenesis
Provisionally accepted
- 1Laval University, Quebec, Canada
- 2CHU de Quebec Research Center, Axe Neuroscience and Department of Molecular Medicine, Laval University,, Quebec, Canada
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Lipid droplets (LDs), once considered inert lipid stores, are now recognized as active regulators of lipid metabolism, stress responses, and protein quality control in the brain. Their dysregulation is increasingly linked to neurodegenerative diseases, notably Parkinson's disease (PD). This review explores the emerging bidirectional relationship between LDs and α-synuclein (α-Syn), a key pathological hallmark of PD. α-Syn can promote LD accumulation by modulating lipid metabolism and inhibiting lipolysis, while LDs can facilitate α-Syn aggregation through specific lipid-protein and membrane interactions. We summarize current evidence on LD structure, function, and dynamics in neuronal and glial cells, and discuss how alterations in lipid composition, oxidative stress, and associated proteins contribute to PD pathology. Understanding the LD-α-Syn interplay reveals new avenues for therapeutic strategies aimed at restoring lipid homeostasis, enhancing LD turnover, and reducing α-Syn toxicity.
Keywords: lipid droplets, alpha-Synuclein, Parkinson's disease, Lipid droplet functions, Lipidmetabolism, Lipid-Alpha-Synuclein interaction, protein aggregation
Received: 06 Aug 2025; Accepted: 07 Nov 2025.
Copyright: © 2025 Idi, Sheta and Oueslati. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Abid Oueslati, abid.oueslati@crchudequebec.ulaval.ca
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