Division of Pharmacology, Guru Nanak College of Pharmaceutical Science and Technology, 157/F Nilgunaj Road, Panihati, Kolkata, 700114, India.
Curr Diabetes Rev. 2023;19(5):e130522204763. doi: 10.2174/1573399818666220513142030.
Alzheimer's disease (AD) is the most common type of dementia that affects the elderly around the world. Chronic type 2 diabetes (T2DM) has been proven to be closely related to neurodegeneration, especially AD. T2DM is characterized by the cell's failure to take up insulin as well as chronic hyperglycemia. In the central nervous system, insulin plays vital regulatory roles, while in chronic hyperglycemia, it leads to the formation and accumulation of advanced glycation end products (AGEs). Inflammation plays a crucial role in development of insulin resistance in AD and T2DM. The microtubule-related protein tau is involved in the pathogenesis of several neurological diseases known as tauopathies, and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Chronic neuroinflammation causes the breakdown of the blood-brain barrier (BBB) observed in tauopathies. The development of pro-inflammatory signaling molecules, such as cytokines, chemokines from glial cells, neurons and endothelial cells, decides the structural integrity of BBB and immune cell migration into the brain. This review highlights the use of antidiabetic compounds as promising therapeutics for AD, and also describes several new pathological molecular mechanisms associated with diabetes that increase AD pathogenesis.
阿尔茨海默病（AD）是世界范围内影响老年人的最常见的痴呆症类型。慢性 2 型糖尿病（T2DM）已被证明与神经退行性变密切相关，尤其是 AD。T2DM 的特征是细胞不能摄取胰岛素以及慢性高血糖。在中枢神经系统中，胰岛素起着至关重要的调节作用，而在慢性高血糖中，它会导致晚期糖基化终产物（AGEs）的形成和积累。炎症在 AD 和 T2DM 中胰岛素抵抗的发展中起着关键作用。微管相关蛋白 tau 参与了几种被称为 tau 病的神经疾病的发病机制，并且在 AD 中发现 tau 异常过度磷酸化并在神经元中积累。慢性神经炎症导致 tau 病中观察到的血脑屏障（BBB）的破坏。促炎信号分子的发展，如来自神经胶质细胞、神经元和内皮细胞的细胞因子和趋化因子，决定了 BBB 的结构完整性和免疫细胞向大脑的迁移。本综述强调了将抗糖尿病化合物用作 AD 有前途的治疗方法，并描述了与糖尿病相关的几种增加 AD 发病机制的新病理分子机制。
