Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine , Complutense University of Madrid , 28040 Madrid , Spain.
Laboratory of Medicinal Chemistry (IQOG, CSIC) , C/Juan de la Cierva 3 , 28006 Madrid , Spain.
Chem Res Toxicol. 2018 Sep 17;31(9):839-842. doi: 10.1021/acs.chemrestox.8b00192. Epub 2018 Aug 27.
ASS234 is a new multitarget molecule with multiple neuroprotective actions that significantly elevate mRNA levels of NRF2 and HSF1 transcriptional factors and of HSP105, HSP90AB1, HSPA1A, HSPA1B, HSPA5, HSPA8, HSPA9, HSP60, DNAJA1, DNAJB1, DNAJB6, DNAJC3, DNAJC5, DNAJC6, HSPB1, HSPB2, HSPB5, HSPB6, HSPB8, and HSP10 heat shock proteins (HSPs) family members in SH-SY5Y cells. This NRF2 and HSF1 overexpression may explain the upregulation of both the antioxidant enzymes previously described and the members of the HSPs family observed. These findings suggest that ASS234 is a potent HSPs inductor, which might be beneficial for preventing protein misfolding aggregation and cell death in Alzheimer's disease and other neurodegenerative diseases.
ASS234 是一种新型的多靶点分子，具有多种神经保护作用，可显著提高 NRF2 和 HSF1 转录因子以及 HSP105、HSP90AB1、HSPA1A、HSPA1B、HSPA5、HSPA8、HSPA9、HSP60、DNAJA1、DNAJB1、DNAJB6、DNAJC3、DNAJC5、DNAJC6、HSPB1、HSPB2、HSPB5、HSPB6、HSPB8 和 HSP10 热休克蛋白 (HSPs) 家族成员的 mRNA 水平。这种 NRF2 和 HSF1 的过表达可能解释了先前描述的抗氧化酶和 HSPs 家族成员的上调。这些发现表明，ASS234 是一种有效的 HSPs 诱导剂，可能有助于预防阿尔茨海默病和其他神经退行性疾病中的蛋白质错误折叠聚集和细胞死亡。
