Departamento de Fisiologia e Biofisica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo 05508-000, Brazil.
Department of Psychiatry & Behavioral Neurosciences, The University of Alabama at Birmingham, Birmingham Alabama 35294, United States.
ACS Chem Neurosci. 2024 Aug 21;15(16):2982-2994. doi: 10.1021/acschemneuro.4c00113. Epub 2024 Jul 15.
Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents. We attribute these effects to BFT's ability to modulate glucose transporters type 1 and 3 (GLUT1 and GLUT3) in the hippocampus, inhibit GSK3 activity in the hippocampus, and modulate the insulin signaling in the hippocampus and entorhinal cortex, as well as reduce the activation of apoptotic pathways (BAX) in the hippocampus. Therefore, BFT emerges as a promising and accessible intervention in the initial treatment of conditions similar to AD.
阿尔茨海默病(AD)是一种复杂的神经退行性过程,也被认为是一种代谢性疾病,因为大脑中的葡萄糖代谢和胰岛素信号通路发生改变,这与糖尿病有相似之处。本研究旨在研究苯磷硫胺(BFT),一种维生素 B1 类似物,在由脑室注射链脲佐菌素(STZ)诱导的散发性阿尔茨海默病样疾病的神经退行性过程早期的治疗效果。用 150mg/kg 的 BFT 补充 7 天,可逆转 STZ 引起的啮齿动物短期和长期记忆认知障碍。我们将这些效果归因于 BFT 调节海马中葡萄糖转运蛋白 1 和 3(GLUT1 和 GLUT3)的能力,抑制海马中的 GSK3 活性,调节海马和内嗅皮层中的胰岛素信号,并减少海马中凋亡途径(BAX)的激活。因此,BFT 作为一种有前途的、易于获得的干预手段,可用于治疗类似 AD 的早期疾病。