Department of Neural Medicine, Second Hospital of Shandong University, Jinan, China.
J Alzheimers Dis. 2012;30(3):531-43. doi: 10.3233/JAD-2012-111985.
Excessive extracellular deposition of amyloid- peptide (Aβ) in the brain is the pathological hallmark of Alzheimer's disease (AD). Cumulative evidence indicates that autophagy is involved in the metabolism of Aβ and pathogenesis of AD. However, the molecular mechanism underlying the pathogenesis of AD is not yet well defined, and there has been no effective treatment for AD. We recently found that long-term treatment with a butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran- 2(3 H)-one (3BDO) increased levels of insulin-degrading enzyme and neprilysin, suppressed autophagy via an mTOR pathway, lowered levels of Aβ, and prevented AD-like cognitive deficits in the AβPP/PS1 double transgenic mouse model. Therefore, our findings suggest that 3BDO may be beneficial in the prevention and treatment of AD.
脑内淀粉样肽（Aβ）的过度细胞外沉积是阿尔茨海默病（AD）的病理标志。越来越多的证据表明自噬参与了 Aβ的代谢和 AD 的发病机制。然而，AD 发病机制的分子机制尚不清楚，也没有有效的 AD 治疗方法。我们最近发现，长期使用丁内酯衍生物 3-苄基-5-((2-硝基苯氧基)甲基)-二氢呋喃-2(3H)-酮（3BDO）可增加胰岛素降解酶和内肽酶的水平，通过 mTOR 途径抑制自噬，降低 Aβ水平，并预防 AβPP/PS1 双转基因小鼠模型的 AD 样认知缺陷。因此，我们的研究结果表明，3BDO 可能有益于 AD 的预防和治疗。
