未折叠蛋白反应
神经保护
内质网
衣霉素
神经营养因子
生物
细胞生物学
神经科学
药理学
受体
生物化学
作者
Ave Eesmaa,Liying Yu,Helka Göös,Tatiana V. Danilova,Kristofer Nõges,Emmi Pakarinen,Markku Varjosalo,Maria Lindahl,Päivi Lindholm,Mart Saarma
摘要
Cerebral dopamine neurotrophic factor (CDNF) is a neurotrophic factor that has beneficial effects on dopamine neurons in both in vitro and in vivo models of Parkinson’s disease (PD). CDNF was recently tested in phase I-II clinical trials for the treatment of PD, but the mechanisms underlying its neuroprotective properties are still poorly understood, although studies have suggested its role in the regulation of endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR). The aim of this study was to investigate the mechanism of action of CDNF through analyzing the involvement of UPR signaling in its anti-apoptotic function. We used tunicamycin to induce ER stress in mice in vivo and used cultured primary neurons and found that CDNF expression is regulated by ER stress in vivo and that the involvement of UPR pathways is important for the neuroprotective function of CDNF. Moreover, we used AP-MS and BiFC to perform the first interactome screening for CDNF and report novel binding partners of CDNF. These findings allowed us to hypothesize that CDNF protects neurons from ER-stress-inducing agents by modulating UPR signaling towards cell survival outcomes.
科研通智能强力驱动
Strongly Powered by AbleSci AI