Department of Pharmacology, Postgraduate Institute of Medical Education and Research, Research Block B, 4th Floor, Room No. 4043, Chandigarh, 160012, India,
Neurol Sci. 2013 Oct;34(10):1719-25. doi: 10.1007/s10072-013-1454-1. Epub 2013 May 14.
Relentless progression of Alzheimer's disease (AD) poses a grave situation for the biomedical community to tackle. Agents starting as hot favorites in clinical trials have failed in later stages and it is time we reconsidered our approaches to intervene the disease. Quite some interesting work in the last decade has introduced a new school of thought which factors in neuronal glycemic imbalance as a major component for the development of AD. Insulin resistance in the brain has brought forward subsequent sequelae which might work towards amyloid accretion and/or tau hyperphosphorylation. It is also pointed out that insulin works by distributing iron to neuronal tissue and an insulin resistant state throws it off gear leading to iron overloading of neurons which is ultimately detrimental. A relatively recent investigation finds the role of c-Jun-N-terminal kinase (JNK3) in AD which also seems to bear a link with insulin resistance.
阿尔茨海默病（AD）的无情进展给生物医药界带来了严峻的挑战。在临床试验中最初备受关注的药物在后期都失败了，现在是我们重新考虑干预这种疾病的方法的时候了。在过去的十年中，相当多有趣的工作引入了一种新的思路，即把神经元糖代谢失衡作为 AD 发展的一个主要因素。大脑中的胰岛素抵抗带来了随后的后果，可能会导致淀粉样蛋白沉积和/或tau 过度磷酸化。有人指出，胰岛素的作用是将铁分配到神经元组织中，而胰岛素抵抗状态会使其失去作用，导致神经元中铁超载，最终造成损害。最近的一项研究发现 c-Jun-N-末端激酶（JNK3）在 AD 中的作用，它似乎也与胰岛素抵抗有关。
