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Updated: Mar 10, 2026
Analyzing the Parkinson's Disease Mouse Model Induced by Adeno-associated Viral Vectors Encoding Human α-Synuclein
Published on: July 29, 2022
MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian
Mingshu Mo1, Yousheng Xiao2, Shuxuan Huang1
1Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangdong, China.
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.
Insights
Parkinson's disease (PD) is linked to alpha-synuclein aggregation. This study identifies specific microRNAs (miRNAs) in mice and human cerebrospinal fluid (CSF) that could serve as potential biomarkers for PD diagnosis and severity prediction.
Area of Science:
- Neuroscience
- Genetics
- Biochemistry
Background:
- Alpha-synuclein gene mutations are implicated in Parkinson's disease (PD) pathogenesis, leading to protein aggregation in the brain.
- MicroRNAs (miRNAs) are known to regulate alpha-synuclein metabolism, but their precise role in synucleinopathies remains incompletely understood.
Purpose of the Study:
- To investigate miRNA expression profiles in a mouse model of alpha-synucleinopathy.
- To identify candidate miRNAs in cerebrospinal fluid (CSF) of PD patients that correlate with disease state.
Main Methods:
- High-throughput deep sequencing was used to analyze small RNA sequences in the midbrain of A53T-alpha-synuclein transgenic mice.
- Expression levels of selected miRNAs were quantified in CSF samples from PD patients and controls.
- Statistical analyses, including ordered logistic regression, were performed to assess correlations.
Main Results:
- A significant number of miRNAs (644) were differentially expressed in the transgenic mice.
- Eleven candidate miRNAs, notably miR-144-5p, miR-200a-3p, and miR-542-3p, were found to be upregulated in both transgenic mice and PD patients' CSF.
- These upregulated miRNAs demonstrated predictive accuracy for PD and correlated with disease severity.
Conclusions:
- Specific miRNAs, including miR-144-5p, miR-200a-3p, and miR-542-3p, are dysregulated in the context of alpha-synucleinopathy.
- These miRNAs show potential as diagnostic biomarkers for Parkinson's disease in human CSF.
- CSF miRNA profiles may offer valuable insights into PD progression and severity.
