Journal of Molecular Neuroscience

, Volume 69, Issue 2, pp 197–214 | Cite as

MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson’s Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway

  • Yizhi Zhang
  • Weiwei Xu
  • Shanji Nan
  • Meiji Chang
  • Jia FanEmail author


Parkinson’s disease (PD), one of the motor system disorders, is characterized by the loss of dopamine-producing brain cells. Accumulating evidence has highlighted the involvement of microRNAs (miRs) in the development and progression of PD. Hence, we aimed at exploring possible effects of miR-326 on the progression of PD in mice in an attempt to elucidate the underlying mechanism associated with the kallikrein-related peptidase 7 (KLK7)–mediated mitogen-activated protein kinase (MAPK) signaling pathway. In order to identify the regulatory relationship between miR-326 and KLK7 and its biological significance in PD, PD mouse models were established and subsequently treated with mimics or inhibitors of miR-326 or siRNA-KLK7. The content of striatal dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3-methoxytyrosine (3-MT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA); positive expression of tyrosine hydroxylase (TH) and inducible nitric oxide synthase (iNOS); and the levels of IL-1, IL-6, TNF-α, INF-γ, and MAPK signaling pathway–related genes were determined accordingly. The results obtained indicated that KLK7 was negatively targeted by miR-326, with lower miR-326 and higher KLK7 detected among PD mice. The overexpression of miR-326 or silencing of KLK7 was demonstrated to increase the content of DA, DOPAC, HVA, 3-MT, SOD, GSH-Px, and TH positive expression, while reducing iNOS positive expression, MDA content and cell apoptosis, as well as inhibited levels of IL-1, IL-6, TNF-α, INF-γ, and mRNA and protein levels of p38, ERK, JNK, and caspase-3. Taken together, these results provided evidence suggesting that miR-326 could inhibit iNOS activation and apoptosis of dopaminergic neurons through inhibiting the MAPK signaling pathway and negatively regulating KLK7 in mice with PD. These findings highlight the potential of miR-326 as a novel target for future PD treatment.


Parkinson’s disease microRNA-326 Kallikrein-related peptidase 7 Mitogen-activated protein kinase signaling pathway Inducible nitric oxide synthase Apoptosis 



Parkinson’s disease


inducible nitric oxide synthase


high-performance liquid chromatography




superoxide dismutase


glutathione peroxidase




tyrosine hydroxylase


kallikrein-related peptidase 7


3,4-dihydroxyphenylacetic acid




terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling


homovanillic acid


mitogen-activated protein kinase


extracellular signal-regulated kinase


c-Jun NH2-terminal protein kinase


3′untranslated region


wild type




phosphate-buffered saline


fetal bovine serum


Ranilla luciferase


negative control


Hanks’ balanced salt solution


specific pathogen-free




reverse transcription quantitative polymerase chain reaction


immunoglobulin G




optimal cutting temperature


bovine serum albumin


glyceraldehyde-3-phosphate dehydrogenase


tetramethylrhodamine isothiocyanate


fluorescein isothiocyanate




double distilled water


polyvinylidene fluoride


tris-buffered saline Tween-20


enhanced chemiluminescence


Sprague Dawley



We would like to acknowledge the helpful comments on this paper received from our reviewers.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of NeurologyThe Second Hospital of Jilin UniversityChangchunPeople’s Republic of China
  2. 2.Department of NeurologyChangchun Central HospitalChangchunPeople’s Republic of China

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