Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Rajasthan, India.
Cell Biochem Funct. 2024 Sep;42(7):e4111. doi: 10.1002/cbf.4111.
Diabetes mellitus (DM) and Alzheimer's disease (AD) rates are rising, mirroring the global trend of an aging population. Numerous epidemiological studies have shown that those with Type 2 diabetes (T2DM) have an increased risk of developing dementia. These degenerative and progressive diseases share some risk factors. To a large extent, the amyloid cascade is responsible for AD development. Neurofibrillary tangles induce neurodegeneration and brain atrophy; this chain reaction begins with hyperphosphorylation of tau proteins caused by progressive amyloid beta (Aβ) accumulation. In addition to these processes, it seems that alterations in brain glucose metabolism and insulin signalling lead to cell death and reduced synaptic plasticity in AD, before the onset of symptoms, which may be years away. Due to the substantial evidence linking insulin resistance in the brain with AD, researchers have coined the name "Type 3 diabetes" to characterize the condition. We still know little about the processes involved, even though current animal models have helped illuminate the links between T2DM and AD. This brief overview discusses insulin and IGF-1 signalling disorders and the primary molecular pathways that may connect them. The presence of GSK-3β in AD is intriguing. These proteins' association with T2DM and pancreatic β-cell failure suggests they might be therapeutic targets for both disorders.
糖尿病（DM）和阿尔茨海默病（AD）的发病率正在上升，反映出全球人口老龄化的趋势。大量的流行病学研究表明，2 型糖尿病（T2DM）患者患痴呆的风险增加。这些退行性和进行性疾病有一些共同的危险因素。在很大程度上，淀粉样蛋白级联反应负责 AD 的发展。神经原纤维缠结导致神经退行性变和脑萎缩；这种连锁反应始于由淀粉样β（Aβ）积累引起的 tau 蛋白的逐渐磷酸化。除了这些过程之外，似乎大脑葡萄糖代谢和胰岛素信号的改变导致 AD 中的细胞死亡和突触可塑性降低，在症状出现之前，这可能需要数年时间。由于有大量证据表明大脑中的胰岛素抵抗与 AD 有关，研究人员创造了“3 型糖尿病”这个名称来描述这种情况。尽管目前的动物模型有助于阐明 T2DM 和 AD 之间的联系，但我们对涉及的过程仍知之甚少。本文简要讨论了胰岛素和 IGF-1 信号通路紊乱以及可能连接它们的主要分子途径。AD 中存在 GSK-3β 这一事实很有趣。这些蛋白与 T2DM 和胰岛β细胞衰竭有关，这表明它们可能是这两种疾病的治疗靶点。
