AUTHOR=Idi Walid , Sheta Razan , Oueslati Abid 

TITLE=Interplay between lipid droplets and alpha-synuclein: implication in Parkinson’s disease pathogenesis

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=Volume 18 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2025.1681039

DOI=10.3389/fnmol.2025.1681039

ISSN=1662-5099

ABSTRACT=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.