Abstract
The present review provides a comprehensive examination of the intricate dynamics between α-synuclein, a protein crucially involved in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and multiple system atrophy, and endogenously-produced bioactive lipids, which play a pivotal role in neuroinflammation and neurodegeneration. The interaction of α-synuclein with bioactive lipids is emerging as a critical factor in the development and progression of neurodegenerative and neuroinflammatory diseases, offering new insights into disease mechanisms and novel perspectives in the identification of potential biomarkers and therapeutic targets. We delve into the molecular pathways through which α-synuclein interacts with biological membranes and bioactive lipids, influencing the aggregation of α-synuclein and triggering neuroinflammatory responses, highlighting the potential of bioactive lipids as biomarkers for early disease detection and progression monitoring. Moreover, we explore innovative therapeutic strategies aimed at modulating the interaction between α-synuclein and bioactive lipids, including the development of small molecules and nutritional interventions. Finally, the review addresses the significance of the gut-to-brain axis in mediating the effects of bioactive lipids on α-synuclein pathology and discusses the role of altered gut lipid metabolism and microbiota composition in neuroinflammation and neurodegeneration. The present review aims to underscore the potential of targeting α-synuclein-lipid interactions as a multifaceted approach for the detection and treatment of neurodegenerative and neuroinflammatory diseases.