White Anthony R, Barnham Kevin J, Bush Ashley I
The University of Melbourne, Department of Pathology, Victoria 3010, Australia.
Expert Rev Neurother. 2006 May;6(5):711-22. doi: 10.1586/14737175.6.5.711.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by neuronal dysfunction and the formation of amyloid plaques in the brain. Although the pathological processes resulting in the onset and progression of AD are not well understood, there is a growing body of evidence to support a central role for biometals in many critical aspects of the illness. Recent reports have described the exciting development of potential therapeutic agents based on the modulation of metal bioavailability. The metal ligand, clioquinol has demonstrated promising results in animal models and small clinical trials and a new generation of metal ligand-based therapeutics are currently under development. However, further research is necessary to fully understand the complex and interdependent pathways of biometal homeostasis and amyloid metabolism in AD. This information will be vital for the development of safe and effective metal-based pharmaceuticals for the treatment of AD and, potentially, other neurodegenerative disorders.
阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征是神经元功能障碍以及大脑中淀粉样斑块的形成。尽管导致AD发病和进展的病理过程尚未完全明了,但越来越多的证据支持生物金属在该疾病许多关键方面发挥核心作用。最近的报告描述了基于调节金属生物利用度的潜在治疗药物的令人兴奋的进展。金属配体氯碘羟喹在动物模型和小型临床试验中已显示出有前景的结果,并且新一代基于金属配体的治疗方法目前正在研发中。然而,有必要进行进一步研究以充分了解AD中生物金属稳态和淀粉样蛋白代谢的复杂且相互依存的途径。这些信息对于开发用于治疗AD以及可能的其他神经退行性疾病的安全有效的金属基药物至关重要。