Abstract
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 oAβ1–42 in BV-2 cells. Transmission electron microscopy images indicated that the morphology of prepared oAβ1–42 was spherical particles. BV-2 cells treated with ALA were incubated with 5(6)-carboxyfluorescein-labeled oAβ1–42 (FAM-oAβ1–42) 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 oAβ1–42.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 oAβ1–42 treatment. Results from the flow cytometry analysis indicated that the CD36 receptor inhibitor significantly attenuated ALA-promoted phagocytosis of FAM-oAβ1–42 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 oAβ1–42 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.
Highlights
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease with cognitive impairment that accounts for more than half of patients with dementia (Knopman et al, 2021)
We confirmed that the increase in fluorescence of the BV-2 cells by alpha-lipoic acid (ALA) was not attributed to ALA itself—rather it was caused by an increased uptake of FAMoAβ1−42 (Figure 2)
We revealed that in addition to antioxidant and anti-inflammatory properties, ALA may enhance the ability of microglia to eliminate oAβ1−42 and subsequently reduce the neurotoxic effect induced by oAβ1−42, which may offer a possible mechanism underlying the prevention of dementia
Summary
Alzheimer’s disease (AD) is an irreversible neurodegenerative disease with cognitive impairment that accounts for more than half of patients with dementia (Knopman et al, 2021). Synaptic alterations are a critical part of neurodegeneration that are strongly correlated with the morphological lesions of AD, neurotoxicities of tau and Aβ, and cognitive impairment, which induce various neurotoxic effects such as increased inflammation, increased oxidative pressure, and subsequently damages the nerve synapses of the brain (Jack et al, 2019; Srivastava et al, 2019; Knopman et al, 2021). These factors gradually alter the microenvironment system of the brain, which becomes unconducive to the survival of nerve cells. This study aimed to investigate the enhancing effect of vitamin-like alpha-lipoic acid (ALA) on phagocytosis of oligomeric beta-amyloid (oAβ)− in BV-2 mouse microglial cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
