LPC (18:1) Modulates Seeded α-Synuclein Aggregation and Associated Cellular Toxicity in a Stable HEK293FT Model

Synucleinopathies are characterized by pathological α-synuclein (α-Syn) aggregation. Our research group previously developed and marketed Porcine Liver Decomposition Product (PLDP) as a functional supplement, yet its underlying molecular mechanisms remain incompletely understood. This study evaluated the effects of LPC (18:1), a constituent of PLDP, on seeded α-Syn aggregation and associated cellular stress responses using a newly established HEK293FT model. A stable α-Syn-expressing HEK293FT cell line, selected for its high sensitivity to exogenous α-Syn fibril seeds, was utilized. In vitro assays showed that LPC (18:1) inhibited α-Syn fibril elongation. In the cellular model, treatment with LPC (18:1) in the micromolar range attenuated seed-induced intracellular α-Syn aggregation, reduced phosphorylated α-Syn (Ser129) accumulation, restored cell viability, and suppressed LDH release. Furthermore, LPC (18:1) reduced intracellular ROS generation and down-regulated the mRNA and protein expression of inflammatory cytokines (IL-6 and IL-1β). These findings indicate that LPC (18:1) modulates seeded α-Syn aggregation and associated toxicity and cytokine responses in an engineered HEK293FT model. They do not establish neuroprotective or anti-inflammatory effects in disease-relevant cells, therapeutic efficacy, or the effects of PLDP as a formulation.