Mechanism for anti-AD effect of approved medicines

转化生长因子(TGF)-B1刺激这种吞噬作用。我们最近报道，当将APP23 AD小鼠模型与表达热休克蛋白（HSP） 70的转基因小鼠杂交时，这些动物显示出较少的AD相关表型。我们在这里研究了香叶酮，一种HSP70表达的诱导剂，对ad相关表型的影响。连续9个月反复口服香叶酮可改善小鼠认知功能，降低AB水平、AB斑块沉积和突触损失。该处理还上调了ab降解酶和TGF-B1的表达，但不影响APP的成熟和分泌酶的活性。这些结果与经过基因修饰过表达HSP70的APP23小鼠相似。单次口服香叶酮可显著提高大鼠海马内直接注射AB的HSP70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.