title: MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Mingshu
authors.initials: M
authors.lastname: Mo
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
authors.forename: Yousheng
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Shuxuan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
authors.forename: Luan
authors.initials: L
authors.lastname: Cen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangdong, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Ann Romney Center for Neurologic Disease, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shaomin
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurology, The Third Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Xinling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Anatomy & Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
authors.forename: Pingyi
authors.initials: P
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000818:Animals; D015415:Biomarkers; D016022:Case-Control Studies; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D066329:Protein Aggregates; D066263:Protein Aggregation, Pathological; D034622:RNA Interference; D059467:Transcriptome; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D066329:Protein Aggregates; D051844:alpha-Synuclein
keywords: A53T mutation; Gerotarget; Parkinson’s disease; deep sequencing; microRNAs