Oncotarget

Research Papers: Gerotarget (Focus on Aging):

MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian

Mingshu Mo, Yousheng Xiao, Shuxuan Huang, Luan Cen, Xiang Chen, Limin Zhang, Qin Luo, Shaomin Li, Xinling Yang, Xian Lin and Pingyi Xu _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:15-28. https://doi.org/10.18632/oncotarget.13905

Metrics: PDF 3867 views  |   HTML 4016 views  |   ?  


Abstract

Mingshu Mo1, Yousheng Xiao2, Shuxuan Huang1, Luan Cen2, Xiang Chen2, Limin Zhang2, Qin Luo3, Shaomin Li4, Xinling Yang3, Xian Lin5 and Pingyi Xu1

1 Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China

2 Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China

3 Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, China

4 Ann Romney Center for Neurologic Disease, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

5 Department of Anatomy & Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China

Correspondence to:

Pingyi Xu, email:

Shaomin Li, email:

Xinling Yang, email:

Xian Lin, email:

Keywords: Parkinson’s disease, A53T mutation, microRNAs, deep sequencing, Gerotarget

Received: May 25, 2016 Accepted: December 01, 2016 Published: December 11, 2016

Abstract

α-synuclein gene mutations can cause α-synuclein protein aggregation in the midbrain of Parkinson’s disease (PD) patients. MicroRNAs (miRNAs) play a key role in the metabolism of α-synuclein but the mechanism involved in synucleinopathy remains unclear. In this study, we investigated the miRNA profiles in A53T-α-synuclein transgenic mice and analyzed the candidate miRNAs in the cerebrospinal fluid (CSF) of PD patients. The 12-month A53T-transgenic mouse displayed hyperactive movement and anxiolytic-like behaviors with α-synuclein aggregation in midbrain. A total of 317,759 total and 289,207 unique small RNA sequences in the midbrain of mice were identified by high-throughput deep sequencing. We found 644 miRNAs were significantly changed in the transgenic mice. Based on the conserved characteristic of miRNAs, we selected 11 candidates from the 40 remarkably expressed miRNAs and explored their expression in 44 CSF samples collected from PD patients. The results revealed that 11 microRNAs were differently expressed in CSF, emphatically as miR-144-5p, miR-200a-3p and miR-542-3p, which were dramatically up-regulated in both A53T-transgenic mice and PD patients, and had a helpful accuracy for the PD prediction. The ordered logistic regression analysis showed that the severity of PD has strong correlation with an up-expression of miR-144-5p, miR-200a-3p and miR-542-3p in CSF. Taken together, our data suggested that miRNAs in CSF, such as miR-144-5p, miR-200a-3p and miR-542-3p, may be useful to the PD diagnosis as potential biomarkers.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 13905