Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IR 19395-4644, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran.
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Trends Endocrinol Metab. 2019 Oct;30(10):692-700. doi: 10.1016/j.tem.2019.07.012. Epub 2019 Aug 7.
Several conditions result in neurodegeneration; among which diabetes mellitus (DM) is of crucial importance. Tau (τ) malfunction is a major pathological process participating in neurodegeneration. Despite extensive considerations, the actual causative link between DM and τ abnormalities remains uncertain thus far. Phosphorylated (p)-τ at Thr-Pro motifs can exist in the two distinct cis and trans conformations. cis is neurotoxic, and is accumulated upon various stress conditions, such as nutrition depletion. We assume that pathogenic cis p-τ is the central mediator of neurodegeneration in DM, and propose why different brain areas give various responses to stress conditions. We herein juxtapose recent approaches in diabetic neurodegeneration and propose a therapeutic target to stop neuronal loss during DM.
几种情况会导致神经退行性病变;其中糖尿病(DM)尤为重要。tau(τ)功能障碍是参与神经退行性病变的主要病理过程。尽管进行了广泛的考虑,但 DM 和 τ 异常之间的实际因果关系迄今仍不确定。在 Thr-Pro 基序处磷酸化(p)-τ可以存在于两种不同的顺式和反式构象中。顺式是神经毒性的,并在各种应激条件下积累,例如营养耗竭。我们假设致病的顺式 p-τ是 DM 中神经退行性变的中心介质,并提出为什么不同的大脑区域对应激条件有不同的反应。在这里,我们将糖尿病神经退行性病变的最新方法并列,并提出一个治疗靶点,以阻止 DM 期间神经元的丢失。