期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms23169489
关键词
CDNF; neurotrophic factor; ER stress; unfolded protein response; dopamine neurons; sympathetic neurons; apoptosis; protein-protein interactions; mechanism of action
资金
- Jane and Aatos Erkko Foundation
- Academy of Finland [343299, 117044]
- Institute of Biotechnology
- Helsinki Institute of Life Science infrastructure
- University of Helsinki
- Academy of Finland (AKA) [117044, 117044] Funding Source: Academy of Finland (AKA)
This study investigates the mechanism of action of CDNF by analyzing the involvement of UPR signaling in its anti-apoptotic function. The findings suggest that CDNF expression is regulated by ER stress and the involvement of UPR pathways is important for its neuroprotective function. Additionally, novel binding partners of CDNF are identified.
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.
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