Mol Genet Metab. 2012 Nov;107(3):630-1. doi: 10.1016/j.ymgme.2012.06.016. Epub 2012 Jul 4.
Tying up two recent lines of experimental evidence may help explain this vital issue. On the one hand, data indicate that cancerous transformations of cells include changes in expression level and/or the functionality of multidrug resistance modulators which then disturb chemotherapy. On the other hand, studies have shown that some of the ABC transporters--at the blood-brain barrier--work as effective efflux pumps for amyloid Aβ peptides. Amyloid Aβ peptides, cut from the amyloid precursor protein of neurons can be assumed to induce brain wide neuronal apoptosis via opening plasma lemma-standing type-1 VDAC/porin channels as shown by in vitro experiments using established neuronal cell lines. However, extrusion of apoptosis inductive Aβ by increased ABC transporter activity at the blood-brain barrier from the brain of cancer survivors might abolish this effect. The hypothesis presented can be read as a clue on what in recent literature is referred to as the inverse association of cancer and Alzheimer disease.
将最近的两条实验证据联系起来可能有助于解释这个重要问题。一方面,数据表明,细胞的癌变转化包括多药耐药调节剂的表达水平和/或功能的变化,然后干扰化疗。另一方面,研究表明,一些 ABC 转运蛋白——在血脑屏障——作为有效的流出泵,用于排出淀粉样蛋白 Aβ 肽。淀粉样蛋白 Aβ 肽是从神经元的淀粉样前体蛋白中切割出来的,可以通过体外实验用已建立的神经元细胞系证明,通过打开质膜立体型 1 VDAC/porin 通道来诱导全脑神经元凋亡。然而,来自癌症幸存者大脑的血脑屏障中 ABC 转运体活性增加将凋亡诱导性 Aβ 挤出大脑可能会消除这种作用。提出的假设可以被解读为最近文献中所谓的癌症和阿尔茨海默病之间的反向关联的线索。