Effects of α-Lipoic Acid on Phagocytosis of Oligomeric Beta-Amyloid(1–42) in BV-2 Mouse Microglial Cells

Background and objectives: This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)(1–42) in BV-2 mouse microglial cells. Methods: An in vitro model was established to investigate phagocytosis of oAβ(1–42) in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ(1–42) was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ(1–42) (FAM-oAβ(1–42)) for 24 h, followed by flow cytometer analysis, western blotting, real-time quantitative PCR, and immunocytochemistry (ICC) analysis to assess the in vitro phagocytosis ability of oAβ(1–42). Results: Alpha-lipoic acid significantly increased messenger RNA (mRNA) expression of the CD36 receptor in BV-2 cells. ICC analysis showed that ALA significantly elevated CD36 protein expression in BV-2 cells both with and without oAβ(1–42) treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ(1–42) in BV-2 cells. Moreover, ICC analysis revealed that ALA caused the translocation of peroxisome proliferator-activated receptor-γ (PPAR-γ), which is known to regulate the expression of CD36 mRNA in BV-2 cells. ALA also elevated both the mRNA and protein expression of cyclooxygenase-2 (COX-2), which is a key enzyme involved in the synthesis of 15-deoxy-(Δ12,14)-prostaglandin J2 in BV-2 cells. Conclusion: We postulated that ALA enhances oAβ(1–42) phagocytosis by upregulating the COX-2/15-deoxy-(Δ12,14)-prostaglandin J2/PPAR-γ/CD36 pathway in BV-2 cells. Finally, future studies should be conducted with an in vivo study to confirm the findings.