Paul R. Ebert Laboratory, School of Biological Sciences, University of Queensland, Brisbane, 4072, Australia.
Mol Neurobiol. 2013 Feb;47(1):399-424. doi: 10.1007/s12035-012-8352-z. Epub 2012 Sep 26.
Alzheimer's disease (AD) and diabetes are among the most common diseases associated with ageing. The pathology of AD is strongly associated with accumulated misfolding proteins that results in neuronal dysfunction within the brain. Diabetes, on the contrary, is characterised by altered insulin signaling that results in reduced glucose uptake, metabolic suppression of energy consuming cells and conversion of glucose to fat in the liver. Despite distinguishing features, these diseases share common elements and may in fact be viewed as fundamentally similar disorders that differ in magnitude of specific traits, primarily affected tissues and time of onset. In this review, we outline the fundamental basis of each of the two diseases and highlight similarities in their pathophysiology. Further ahead we will discuss these features in relation to the development of drugs to treat these two diseases, particularly AD, for which the development of therapeutic chemicals has proven to be particularly difficult. We conclude with comments on efforts to develop a simple organism, Caenorhabditis elegans, as a genetic model to be used to study the systems biology of diabetes and AD.
阿尔茨海默病(AD)和糖尿病是与衰老相关的最常见疾病之一。AD 的病理学与积累的错误折叠蛋白密切相关,导致大脑内神经元功能障碍。相反,糖尿病的特征是胰岛素信号改变,导致葡萄糖摄取减少、耗能细胞代谢抑制以及肝脏内葡萄糖转化为脂肪。尽管具有不同的特征,但这些疾病具有共同的特征,实际上可以被视为基本相似的疾病,其差异在于特定特征的程度、主要受影响的组织和发病时间。在这篇综述中,我们概述了这两种疾病的基本基础,并强调了它们在病理生理学上的相似之处。进一步,我们将讨论这些特征与治疗这两种疾病的药物的开发的关系,特别是 AD,因为开发治疗性化学物质被证明是特别困难的。最后,我们对开发简单生物体秀丽隐杆线虫作为研究糖尿病和 AD 系统生物学的遗传模型的努力进行了评论。