Biometals and Their Therapeutic Implications in Alzheimer’s Disease

被引:0
作者
Scott Ayton
Peng Lei
Ashley I. Bush
机构
[1] The University of Melbourne,Oxidation Biology Unit, Florey Institute of Neuroscience and Mental Health
来源
Neurotherapeutics | 2015年 / 12卷
关键词
Alzheimer’s disease; Iron; Copper; Zinc; Chelation therapy;
D O I
暂无
中图分类号
学科分类号
摘要
No disease modifying therapy exists for Alzheimer’s disease (AD). The growing burden of this disease to our society necessitates continued investment in drug development. Over the last decade, multiple phase 3 clinical trials testing drugs that were designed to target established disease mechanisms of AD have all failed to benefit patients. There is, therefore, a need for new treatment strategies. Changes to the transition metals, zinc, copper, and iron, in AD impact on the molecular mechanisms of disease, and targeting these metals might be an alternative approach to treat the disease. Here we review how metals feature in molecular mechanisms of AD, and we describe preclinical and clinical data that demonstrate the potential for metal-based drug therapy.
引用
收藏
页码:109 / 120
页数:11
相关论文
共 771 条
  • [1] Hardy JA(1992)Alzheimer’s disease: the amyloid cascade hypothesis Science 256 184-185
  • [2] Higgins GA(1985)Amyloid plaque core protein in Alzheimer disease and Down syndrome Proc Natl Acad Sci U S A 82 4245-4249
  • [3] Masters CL(1986)Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease Proc Natl Acad Sci U S A 83 4044-4048
  • [4] Simms G(1987)Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus Science 235 880-884
  • [5] Weinman NA(1999)Membrane-anchored aspartyl protease with Alzheimer’s disease beta-secretase activity Nature 402 533-537
  • [6] Multhaup G(1999)Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity Nature 398 513-517
  • [7] McDonald BL(2009)Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: a randomized controlled trial JAMA 302 2557-2264
  • [8] Beyreuther K(2013)A phase 3 trial of semagacestat for treatment of Alzheimer’s disease N Engl J Med 369 341-350
  • [9] Kosik KS(2014)Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease N Engl J Med 370 311-321
  • [10] Joachim CL(2014)Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease N Engl J Med 370 322-333