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MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian.
Oncotarget. 2017 Jan 03; 8(1):15-28.O

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.

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Authors+Show Affiliations

Mo M
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
Xiao Y
Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
Huang S
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
Cen L
Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
Chen X
Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
Zhang L
Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
Luo Q
Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Li S
Ann Romney Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Yang X
Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Lin X
Department of Anatomy & Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
Xu P
Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.

MeSH

AdultAgedAllelesAnimalsBiomarkersCase-Control StudiesDisease Models, AnimalDopaminergic NeuronsFemaleGene Expression ProfilingGene Expression RegulationHigh-Throughput Nucleotide SequencingHumansHyperkinesisMaleMiceMice, TransgenicMicroRNAsMiddle AgedMutationParkinson DiseaseProtein AggregatesProtein Aggregation, PathologicalRNA InterferenceTranscriptomealpha-Synuclein

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27965467

Citation

Mo, Mingshu, et al. "MicroRNA Expressing Profiles in A53T Mutant Alpha-synuclein Transgenic Mice and Parkinsonian." Oncotarget, vol. 8, no. 1, 2017, pp. 15-28.
Mo M, Xiao Y, Huang S, et al. MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian. Oncotarget. 2017;8(1):15-28.
Mo, M., Xiao, Y., Huang, S., Cen, L., Chen, X., Zhang, L., Luo, Q., Li, S., Yang, X., Lin, X., & Xu, P. (2017). MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian. Oncotarget, 8(1), 15-28. https://doi.org/10.18632/oncotarget.13905
Mo M, et al. MicroRNA Expressing Profiles in A53T Mutant Alpha-synuclein Transgenic Mice and Parkinsonian. Oncotarget. 2017 Jan 3;8(1):15-28. PubMed PMID: 27965467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian. AU - Mo,Mingshu, AU - Xiao,Yousheng, AU - Huang,Shuxuan, AU - Cen,Luan, AU - Chen,Xiang, AU - Zhang,Limin, AU - Luo,Qin, AU - Li,Shaomin, AU - Yang,Xinling, AU - Lin,Xian, AU - Xu,Pingyi, PY - 2016/05/25/received PY - 2016/12/01/accepted PY - 2016/12/15/pubmed PY - 2018/3/6/medline PY - 2016/12/15/entrez KW - A53T mutation KW - Gerotarget KW - Parkinson’s disease KW - deep sequencing KW - microRNAs SP - 15 EP - 28 JF - Oncotarget JO - Oncotarget VL - 8 IS - 1 N2 - 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. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/27965467/MicroRNA_expressing_profiles_in_A53T_mutant_alpha_synuclein_transgenic_mice_and_Parkinsonian_ DB - PRIME DP - Unbound Medicine ER -