Bandyopadhyay S, Huang X, Cho H, Greig N H, Youdim M B, Rogers J T
Neurochemistry Laboratory, Department of Psychiatry, Genetics and Aging Research Unit, Massachusetts General Hospital 2 NIA, Baltimore, MD, USA.
J Neural Transm Suppl. 2006(71):237-47. doi: 10.1007/978-3-211-33328-0_25.
Iron closely regulates the expression of the Alzheimer's Amyloid Precursor Protein (APP) gene at the level of message translation by a pathway similar to iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive Elements in their 5' untranslated regions (5'UTRs). Using transfection based assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which iron, copper and zinc up-regulate IRE activity in the APP 5'UTR. Desferrioxamine (high affinity Fe3+ chelator), (ii) clioquinol (low affinity Fe/Cu/Zn chelator), (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested for their relative modulation of APP 5' UTR directed translation of a luciferase reporter gene. Iron chelation based therapeutic strategies for slowing the progression of Alzheimer's disease (and other neurological disorders that manifest iron imbalance) are discussed with regard to the relative neural toxic action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells.
铁通过一条类似于铁对铁蛋白L和H mRNA在其5'非翻译区（5'UTR）的翻译进行控制的途径，在信息翻译水平上紧密调节阿尔茨海默病淀粉样前体蛋白（APP）基因的表达。我们利用基于转染的实验，在SH-SY5Y神经母细胞瘤细胞中测试了铁、铜和锌上调APP 5'UTR中IRE活性的相对效率。测试了去铁胺（高亲和力Fe3+螯合剂）、氯碘羟喹（低亲和力Fe/Cu/Zn螯合剂）、哌嗪-1（口服铁螯合剂）、VK-28（口服铁螯合剂）对APP 5'UTR指导的荧光素酶报告基因翻译的相对调节作用。针对每种螯合剂在SH-SY5Y细胞和H4胶质母细胞瘤细胞中的相对神经毒性作用，讨论了基于铁螯合的治疗策略，以减缓阿尔茨海默病（以及其他表现出铁失衡的神经疾病）的进展。
