DEGRADATION OF ABNORMAL PROTEIN/ANTIAGRIGATION SUBSTANCE, REGARDING ENDOPLASMIC RETICULUM ASSOCIATED MOLECULE AS A TARGET OF THERAPEUTIC AGENT ON NEURODEGERERATIVE DISEASE

泛素连接酶（E3）HRD 1蛋白水平在阿尔茨海默病（AD）患者的大脑皮层中显著降低，这些患者的大脑处于ER应激状态。此外，HRD 1水平与Aβ水平呈负相关。本研究揭示HRD 1水平的降低是由于其不溶解。活性氧（ROS）诱导的HRD 1和SEL 1 L不溶解可能参与AD发病机制中Aβ的产生。神经干/祖细胞（Neural stem/progenitor cells，NSCs）位于成年哺乳动物海马齿状回的脑室下区（subventricular zone，SVZ）和颗粒下区（subgranular zone）。我们发现HRD 1在成人脑的神经干细胞中的定位。我们发现，几个4-苯基丁酸1（4-PBA）衍生物表现出抗聚集活性的化学伴侣活性高于4-PBA。

The ubiquitin ligase(E3) HRD1 protein levels were significantly decreased in the cerebral cortex of patients with Alzheimer's disease(AD), and that the brains of these patients were under ER stress. Furthermore, HRD1 levels negatively correlated with Aβlevels. The present study revealed that the decrease in HRD1 levels was due to its insolubilization. A reactive oxygen species(ROS)-induced insolubilization of HRD1 and SEL1L may be involved in Aβgeneration in the pathogenesis of AD. Neural stem/progenitor cells(NSCs) reside in the subventricular zone(SVZ) and subgranular zone of the hippocampal dentate gyrus in adult mammals. We found the localization of HRD1 in the NSCs of the adult brain. We found that several 4-phenylbutyric acid 1(4-PBA) derivatives demonstrated anti-aggregation activity as a chemical chaperone activity higher than that of 4-PBA.