Open AccessEchinacoside's nigrostriatal dopaminergic protection against 6‐OHDA‐Induced endoplasmic reticulum stress through reducing the accumulation of Seipin
Author(s) -
Zhang Yajie,
Long Hongyan,
Zhou Fuqiong,
Zhu Weina,
Ruan Jie,
Zhao Yang,
Lu Yan
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13285
Subject(s) - chemistry , dopaminergic , endoplasmic reticulum , tyrosine hydroxylase , microbiology and biotechnology , oxidative stress , in vivo , pharmacology , biochemistry , dopamine , biology , endocrinology , enzyme
Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent epidemiological studies suggest that echinacoside (ECH), a phenylethanoid glycoside found in Cistanche deserticola , has a protective effect against the development of PD. However, the detailed mechanisms of how ECH suppresses neuronal death have not been fully elucidated. In this study, we confirmed that ECH protects nigrostriatal neurons against 6‐hydroxydopamine (6‐OHDA)‐induced endoplasmic reticulum stress (ERS) in vivo and in vitro . ECH rescued cell viability in damaged cells and decreased 6‐OHDA‐induced reactive oxygen species accumulation in vitro . It also rescued tyrosine hydroxylase and dopamine transporter expression in the striatum, and decreased α‐synuclein aggregation following 6‐OHDA treatment in vivo . The validated mechanism of ECH activity was the reduction in the 6‐OHDA‐induced accumulation of seipin (Berardinelli–Seip congenital lipodystrophy 2). Seipin has been shown to be a key molecule related to motor neuron disease and was tightly associated with ERS in a series of in vivo studies. ECH attenuated seipinopathy by promoting seipin degradation via ubiquitination. ERS was relieved by ECH through the Grp94/Bip‐ATF4‐CHOP signal pathway.