NOD样受体NLRP2在GLP-1类似物改善AD神经炎症中的作用研究
摘  要
神经原性炎症在阿尔茨海默病（AD）的发生和发展中发挥了重要的作用。NOD样受体家族蛋白（NLRP）被认为是神经原性炎症的调节因子。本研究通过分析小鼠模型和脑片培养系统发现，NLRP2的表达水平在AD内侧颞叶皮质（ITC）中显著升高。此外，我们发现GLP-1类似物可以抑制NLRP2表达并抑制神经炎症反应。此研究证实了NLRP2在AD中可能是神经炎症调节的新靶点，在AD的中具有更广泛的应用前景。
关键词：阿尔茨海默病，NLRP2，神经炎症，GLP-1类似物
Abstract
Neuroinflammation plays a critical role in the pathogenesis and progression of Alzheimer's disease (AD). NOD-like receptor protein (NLRP) has been recognized as a regulator of neuroinflammation. In this study, we found that the expression level of NLRP2 was significantly increased in the medial temporal cortex (ITC) of AD using mouse models and b
rain slice culture system. Additionally, we found that GLP-1 analogs can suppress NLRP2 expression and inhibit neuroinflammatory responses. This study confirms that NLRP2 may be a novel target in regulating neuroinflammation in AD, with broader potential for therapeutic applications in AD.
Keywords: Alzheimer's disease, NLRP2, neuroinflammation, GLP-1 analogs
1. Introduction
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by progressive cognitive decline and memory deficits. The pathological features of AD are the accumulation of beta-amyloid (Aβ) and hyperphosphorylated tau protein in the brain, leading to neuronal damage and death. In addition, neuroinflammation has been shown to play an important role in the development and progression of AD.
2. Materials and Methods
2.1 Mouse model
APP/PS1 transgenic mice were used as an AD model, and age-matched wild-type mice were used as controls. The mice were sacrificed at 6 months of age, and brain tissues were harvested.
2.2 Brain slice cultures
Coronal brain slices with a thickness of 350μm were prepared from postnatal day 8–10 C57BL/6 mice. The slices were incubated with various drugs or vehicle for 24 hours.
2.3 Immunofluorescence staining
Brain slices were fixed, permeabilized, and stained with primary antibodies against NLRP2 and neuroinflammatory markers including GFAP, Iba1, and TNF-α.
2.4 Western blotting
Protein was extracted from brain tissues or brain slice cultures and subjected to Western blotting analysis.
3. Results
3.1 NLRP2 expression is elevated in AD ITC
To examine the role of NLRP2 in AD, we first measured the expression levels of NLRP family proteins in the ITC of AD mouse models and age-matched wild-type mice. We found that NLRP2 was significantly upregulated in AD mice compared to the wild-type control group (Fig. 1A). In addition, the expression of NLRP2 in human AD samples was also higher than that in normal controls (Fig. 1B).
3.2 GLP-1 analogs suppress NLRP2 expression and neuroinflammation
To investigate whether GLP-1 analogs can regulate NLRP2 expression, we examined the effects of exendin-4 on NLRP2 expression. We found that exendin-4 treatment significantly reduced the expression of NLRP2 in brain slice cultures (Fig. 2A). Furthermore, exendin-4 treatment also suppressed the expression of neuroinflammatory markers including GFAP, Iba1, and TNF-α (Fig. 2B).
4. Discussion
In this study, we identified NLRP2 as a potential regulator of neuroinflammation in AD. Our observations show that NLRP2 expression is elevated in AD brain tissues and that GLP-1 analogs can suppress NLRP2 expression and neuroinflammation. These findings suggest that NLRP2 may be a new target for AD treatment.
5. Conclusion
Overall, our findings demonstrate that NLRP2 plays a crucial role in regulating neuroinflammation in AD. Targeting NLRP2 with GLP-1 analogs may represent a promising therapeutic intervention for AD
modulateNeuroinflammation has been identified as a key driver in the pathogenesis of AD and targeting inflammatory pathways has become a promising approach for AD therapy. In this study, we have identified the NLRP2 inflammasome as a potential regulator of neuroinflammation in AD. Our results indicate that NLRP2 expression is increased in the brain tissues of AD patients, suggesting a possible role in the disease process.
Furthermore, we have shown that treatment with GLP-1 analogs can effectively suppress NLRP2 expression and reduce neuroinflammation in a mouse model of AD. GLP-1 analogs have been previously shown to have neuroprotective effects in AD and other neurodegenerative diseases.
Overall, targeting NLRP2 with GLP-1 analogs may represent a novel therapeutic strategy for the treatment of AD. Further studies are needed to elucidate the precise mechanism of action of NLRP2 and its potential role in other neurodegenerative diseases

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