Triggering receptor expressed on myeloid cells 2 (TREM2) is a membrane receptor on myeloid cells and plays an important role in the body's immune defense. Recently, TREM2 has received extensive attention from researchers, and its activity has been found in Alzheimer's disease, neuroinflammation, and traumatic brain injury. The appearance of TREM2 is usually accompanied by changes in apolipoprotein E (ApoE), and there has been a lot of research into their structure, as well as the interaction mode and signal pathways involved in them. As two molecules with broad and important roles in the human body, understanding their correlation may provide therapeutic targets for certain diseases. In this article, we reviewed several diseases in which TREM2 and ApoE are synergistically involved in the development. We further discussed the positive or negative effects of the TREM2–ApoE pathway on nervous system immunity and inflammation.

Lipid droplets (LDs) are the organelles for storing neutral lipids, which are broken down when energy is insufficient. It has been suggested that excessive accumulation of LDs can affect cellular function, which is important to coordinate homeostasis of lipids in vivo. Lysosomes play an important role in the degradation of lipids, and the process of selective autophagy of LDs through lysosomes is known as lipophagy. Dysregulation of lipid metabolism has recently been associated with a variety of central nervous system (CNS) diseases, but the specific regulatory mechanisms of lipophagy in these diseases remain to be elucidated. This review summarizes various forms of lipophagy and discusses the role that lipophagy plays in the development of CNS diseases in order to reveal the related mechanisms and potential therapeutic targets for these diseases.

Background The process of neuroinflammation is marked by the production of pro-inflammatory cytokines and leads to neuronal death. However, accumulating evidence suggests that classic inflammatory processes alone do not fully explain many aspects of neuroinflammation pathogenesis. Recent findings indicate that abnormal deposition of lipid droplet (LD) plays a crucial role in the pathogenesis of neuroinflammation. Microglia, which regulate neuronal activity have been implicated in LD aggregation during neuroinflammation. However, the regulatory mechanism of LDs in neurons remains poorly understood. Methods Neurons were stimulated with LPS-treated microglia supernatant. Immunostaining with BODIPY was used to determine the localization of LDs in different neuronal cell lines and culture systems. LAMP and LC3 were used as lysosomal markers for LD co-localization analysis. For in vivo studies, we used a sepsis-associated encephalopathy (SAE) mouse model to mimic neuroinflammation. Following microglia depletion using the small molecule CSF-1R inhibitor PLX3397, we examined lactate levels and LD changes in the mouse hippocampus. Results Our findings revealed activated microglia caused LD aggregation in neurons inducted by lactate. Furthermore, we observed co-localization of LDs with LAMP2 and LC3, suggesting involvement of the lysosomal pathway. These results were corroborated in an in vivo SAE model, where PLX3397 administration led to a reduction in LD accumulation and lactic acid levels. Conclusion Our study demonstrated that activated microglia induce LD accumulation in various neuronal cultures via the lactate-lysosome signaling pathway. A better understanding of the neuron lipid metabolism in the nervous system may ultimately contribute to the development of novel therapeutic strategies for neuroinflammation.

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