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Updated: Aug 9, 2025
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
ACSL4 promotes microglia-mediated neuroinflammation by regulating lipid metabolism and VGLL4 expression
Xin Zhou1, Rui Zhao2, Mengfei Lv1
1Institute of Neuroregeneration and Neurorehabilitation, Qingdao University, Ningxia Road 308, Qingdao 266071, Shandong, China; Qingdao Medical College, Qingdao University, Qingdao 266071, China.
Abstract:
Acyl-CoA synthetase long-chain family member 4 (ACSL4) is an important isozyme in polyunsaturated fatty acid (PUFA) metabolism. The role of ACSL4 in the lipopolysaccharide (LPS)-induced inflammation of microglia, and the effects of ACSL4-mediated inflammation on the progression of Parkinson's disease (PD) are unknown. In this study, we found that ACSL4 expression was increased after LPS stimulation. Knocking down ACSL4 in microglia decreased proinflammatory cytokine production. Mechanistically, ACSL4 reduced vestigial-like family member 4(VGLL4) expression to promote NF-κB signal transduction; and ACSL4 regulated lipid composition after LPS stimulation. In addition, knocking down ACSL4 alleviated neuroinflammation in a systemic LPS model and acute l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) model. These data revealed ACSL4 to be a novel regulator that promotes microglia-mediated neuroinflammation by regulating VGLL4 expression and lipid metabolism.
Insights
Acyl-CoA synthetase (ACSL4) promotes neuroinflammation in Parkinson's disease by regulating microglial responses. Inhibiting ACSL4 reduces inflammation and alleviates disease progression in models.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Acyl-CoA synthetase long-chain family member 4 (ACSL4) is crucial for polyunsaturated fatty acid (PUFA) metabolism.
- The specific roles of ACSL4 in microglial inflammation and Parkinson's disease (PD) pathogenesis remain unclear.
Purpose of the Study:
- To investigate the function of ACSL4 in lipopolysaccharide (LPS)-induced microglial inflammation.
- To determine the impact of ACSL4-mediated inflammation on Parkinson's disease progression.
Main Methods:
- Assessed ACSL4 expression following LPS stimulation in microglia.
- Utilized ACSL4 knockdown in microglial cells to evaluate its effect on cytokine production.
- Investigated the molecular mechanism involving vestigial-like family member 4 (VGLL4) and NF-κB signaling.
- Examined lipid composition changes post-LPS stimulation.
- Evaluated the therapeutic potential of ACSL4 inhibition in systemic LPS and MPTP-induced PD models.
Main Results:
- ACSL4 expression significantly increased upon LPS stimulation.
- Knockdown of ACSL4 diminished the production of proinflammatory cytokines in microglia.
- ACSL4 was found to downregulate VGLL4 expression, thereby enhancing NF-κB signaling.
- ACSL4 influenced lipid metabolism following LPS exposure.
- Reducing ACSL4 levels ameliorated neuroinflammation in established PD models.
Conclusions:
- ACSL4 acts as a novel regulator that exacerbates microglia-driven neuroinflammation.
- ACSL4 promotes neuroinflammation by modulating VGLL4 expression and altering lipid metabolism.
- Targeting ACSL4 may offer a therapeutic strategy for Parkinson's disease by reducing neuroinflammation.
