Mechanism for anti-AD effect of approved medicines

转化生长因子-β1刺激这种吞噬作用。我们最近报道，当APP23小鼠模型与表达热休克蛋白(HSP)70的转基因小鼠杂交时，这些动物显示的AD相关表型较少。我们在这里研究了香叶基香叶内酮对AD相关表型的影响，香叶基香叶内酮是HSP70表达的诱导剂。APP23小鼠反复口服香叶基香叶内酮9个月，不仅能改善认知功能，还能减少AB、AB斑块沉积和突触丢失。该处理还上调了AB降解酶和转化生长因子-β1的表达，但不影响APP的成熟和分泌酶的活性。这些结果与在过表达HSP70的APP23转基因小鼠中观察到的结果相似。当AB直接注射到海马区时，单次口服香叶基香叶内酮显著增加了HSP70的水平。

Transforming growth factor (TGF)-B1 stimulates this phagocytosis. We recently reported that the APP23 mouse model for AD showed fewer AD-related phenotypes when these animals were crossed with transgenic mice expressing heat shock protein (HSP) 70. We here examined the effect of geranylgeranylacetone, an inducer of HSP70 expression, on the AD-related phenotypes. Repeated oral administration of geranylgeranylacetone to APP23 mice for 9 months not only improved cognitive function but also decreased levels of AB, AB plaque deposition and synaptic loss. The treatment also up-regulated the expression of an AB-degrading enzyme and TGF-B1 but did not affect the maturation of APP and secretase activities. These outcomes were similar to those observed in APP23 mice genetically modified to overexpress HSP70. A single oral administration of geranylgeranylacetone significantly increased the level of HSP70 when AB was concomitantly injected directly into the hippocampus.