Abstract
Parkinson’s disease is a neurodegenerative disorder with an inflammatory response as the core pathogenic mechanism. Previous human genetics findings support the view that the loss of TREM2 function will aggravate neurodegeneration, and TREM2 is one of the most highly expressed receptors in microglia. However, the role of TREM2 in the inflammatory mechanism of PD is not clear. In our study, it was found both in vivo and in vitro that the activation of microglia not only promoted the secretion of inflammatory factors but also decreased the level of TREM2 and inhibited the occurrence of autophagy. In contrast, an increase in the level of TREM2 decreased the expression of inflammatory factors and enhanced the level of autophagy through the p38 MAPK/mTOR pathway. Moreover, increased TREM2 expression significantly decreased the apoptosis of dopaminergic (DA) neurons and improved the motor ability of PD mice. In summary, TREM2 is an important link between the pathogenesis of PD and inflammation. Our study provides a new view for the mechanism of TREM2 in PD and reveals TREM2 as a potential therapeutic target for PD.
Highlights
Parkinson’s disease is a neurodegeneration with the mechanism of central inflammation at its core (Subhramanyam et al, 2019; Pajares et al, 2020)
We evaluated the expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) in BV2 cell lines induced by lipopolysaccharide (LPS) and found that TREM2 expression increased briefly after the cells were stimulated by LPS for a short period of time, and the expression level of TREM2 mRNA decreased with time (Figure 1A) (p < 0.05)
The results showed that the TREM2 protein level decreased significantly under LPS treatment (Figure 1D) (p < 0.01), and so did the expression of mRNA (Figure 1B) (p < 0.05)
Summary
Parkinson’s disease is a neurodegeneration with the mechanism of central inflammation at its core (Subhramanyam et al, 2019; Pajares et al, 2020). Research on microglia has gradually become the focus of Parkinson’s disease research (Tang and Le, 2016). Microglia are a innate immune cell, and immune inflammation mediated by microglia should be associated with Parkinson’s disease (Kannarkat et al, 2013; Heneka et al, 2014). The activation of microglia leads to an increase in the levels of ROS. The Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) gene, located on human chromosome 6 and mouse chromosome 17, encodes an innate immune receptor of the immunoglobulin family (Washington et al, 2002). The signal is terminated by TREM2 ectodomain shedding and subsequent intramembrane cleavage by γ-secretase (Steiner et al, 2020)
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