期刊
PHYTOMEDICINE
卷 102, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2022.154193
关键词
Parkinson's disease; Dendrobine; MANF; ER stress; Dopaminergic neuron
资金
- National Natural Science Foundation of China [32070386, U19A2009]
- Project for Science and Technology Research Plan from Anhui Province of China [201903a07020020]
- Natural Science Foundation of Anhui Province [1908085QH323]
- University Natural Science Key Research Program of Anhui Province [KJ2021A0208]
Dendrobine has an antiparkinsonian effect by facilitating MANF-mediated ER stress suppression, reducing motor impairments and dopaminergic neuron apoptosis in a PD mouse model.
Background: Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. Purpose: This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. Methods: Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. Results: Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. Conclusion: Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据