Premium
MicroRNA‐326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease
Author(s) -
Zhao XiaoHui,
Wang YongBing,
Yang Juan,
Liu HuiQin,
Wang LingLing
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28761
Subject(s) - xbp1 , autophagy , dopaminergic , substantia nigra , parkinson's disease , microrna , microbiology and biotechnology , signal transduction , nitric oxide synthase , chemistry , biology , endocrinology , dopamine , medicine , nitric oxide , biochemistry , disease , apoptosis , rna , rna splicing , gene
Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR‐326 in PD through the JNK signaling pathway by targeting X‐box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR‐326 and XBP1 was confirmed. The expression of miR‐326 and XBP1 was measured in PD mice, and gain‐ and loss‐function assay was conducted to examine the regulatory effect of miR‐326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR‐326 mimic and siRNA‐XBP1 showed increased traction test scores, activation of autophagy, expression of LC3‐II, c‐Jun, and p‐α‐Syn, but diminished climbing time and expressions of iNOS, α‐Syn, and p‐c‐Jun. The siRNA‐XBP1 treatment could reverse the effect of miR‐326 inhibitor on PD mice. Overexpression of miR‐326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.