Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain.
Front Endocrinol (Lausanne). 2022 May 9;13:873301. doi: 10.3389/fendo.2022.873301. eCollection 2022.
Several neurological diseases share pathological alterations, even though they differ in their etiology. Neuroinflammation, altered brain glucose metabolism, oxidative stress, mitochondrial dysfunction and amyloidosis are biological events found in those neurological disorders. Altered insulin-mediated signaling and brain glucose hypometabolism are characteristic signs observed in the brains of patients with certain neurological diseases, but also others such as type 2 diabetes mellitus and vascular diseases. Thus, significant reductions in insulin receptor autophosphorylation and Akt kinase activity, and increased GSK-3 activity and insulin resistance, have been reported in these neurological diseases as contributing to the decline in cognitive function. Supporting this relationship is the fact that nasal and hippocampal insulin administration has been found to improve cognitive function. Additionally, brain glucose hypometabolism precedes the unmistakable clinical manifestations of some of these diseases by years, which may become a useful early biomarker. Deficiencies in the major pathways of oxidative energy metabolism have been reported in patients with several of these neurological diseases, which supports the hypothesis of their metabolic background. This review remarks on the significance of insulin and brain glucose metabolism alterations as keystone common pathogenic substrates for certain neurological diseases, highlighting new potential targets.
几种神经退行性疾病具有共同的病理改变，尽管它们的病因不同。神经炎症、脑葡萄糖代谢改变、氧化应激、线粒体功能障碍和淀粉样变性是在这些神经退行性疾病中发现的生物学事件。在某些神经退行性疾病患者的大脑中观察到胰岛素介导的信号改变和脑葡萄糖代谢低下，这是特征性标志，但在 2 型糖尿病和血管疾病等其他疾病中也观察到这种情况。因此，在这些神经退行性疾病中，已经报道了胰岛素受体自身磷酸化和 Akt 激酶活性的显著降低，以及 GSK-3 活性的增加和胰岛素抵抗，这有助于认知功能的下降。支持这种关系的事实是，鼻内和海马胰岛素给药已被发现可改善认知功能。此外，脑葡萄糖代谢低下先于这些疾病的某些明确临床症状出现数年，这可能成为一种有用的早期生物标志物。在这些神经退行性疾病患者中已经报道了几种主要氧化能量代谢途径的缺陷，这支持了它们的代谢背景假说。这篇综述强调了胰岛素和脑葡萄糖代谢改变作为某些神经退行性疾病共同关键致病底物的重要性，突出了新的潜在靶点。
