4.1 Article

Compound AD16 Reduces Amyloid Plaque Deposition and Modifies Microglia in a Transgenic Mouse Model of Alzheimer's Disease

期刊

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
卷 3, 期 6, 页码 1100-1110

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsptsci.0c00073

关键词

AD16; Alzheimer's disease; lysosome; microglia; senescent cell

资金

  1. Natural Science Foundation of Guangdong Province, China [2017A030310171, 2016A030313167]
  2. National Natural Science Foundation of China [81872743]
  3. Guangzhou Science and Technology Program General project [20180304001]
  4. Science and Technology Planning Project of Guangdong Province [2017B030314056]
  5. Guangzhou Medical University [G2016013]

向作者/读者索取更多资源

Microglial dysfunction is involved in the pathological cascade of Alzheimer's disease (AD). The regulation of microglial function may be a novel strategy for AD therapy. We previously reported the discovery of AD16, an antineuroinflammatory molecule that could improve learning and memory in the AD model. Here, we studied its properties of microglial modification in the AD mice model. In this study, AD16 reduced interleukin-1 beta (IL-1 beta) expression in the lipopolysaccharide-induced IL-1 beta-Luc transgenic mice model. Compared with mice receiving placebo, the group treated with AD16 manifested a significant reduction of microglial activation, plaque deposition, and peri-plaques microgliosis, but without alteration of the number of microglia surrounding the plaque. We also found that AD16 decreased senescent microglial cells marked with SA-beta-gal staining. Furthermore, altered lysosomal positioning, enhanced Lysosomal Associated Membrane Protein 1 (LAMP1) expression, and elevated adenosine triphosphate (ATP) concentration were found with AD16 treatment in lipopolysaccharide-stimulated BV2 microglial cells. The underlying mechanisms of AD16 might include regulating the microglial activation/senescence and recovery of its physiological function via the improvement of lysosomal function. Our findings provide new insights into the AD therapeutic approach through the regulation of microglial function and a promising lead compound for further study.

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