Abstract
MicroRNAs (miRNAs) are endogenous small (18–25 nt), single-stranded, non-coding RNAs that play key roles in post-transcriptional gene expression regulation. The expression profiles of miRNAs in biofluids and tissues change in various diseases. Multiple system atrophy (MSA) and Parkinson’s disease (PD) are both categorized as α-synucleinopathies and often present with similar clinical manifestations. This study aimed to identify miRNAs that are differently expressed in plasma samples of PD patients, MSA patients, and healthy controls. We used microarray analysis to screen for miRNAs that are up- and down-regulated in these patients and analyzed the relative-quantitative expression levels of the identified miRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p showed significantly different expression levels among patients with MSA-C, MSA-P, or PD, and healthy controls. Hsa-miR-671-5p levels were lower in the MSA-P and PD than the MSA-C and control groups, hsa-miR-19b-3p levels were higher in the PD than the other groups, and hsa-miR-24-3p levels were higher in the PD than the MSA-C group. Hsa-miR-671-5p was the first miRNA shown to be expressed differently between MSA-C and MSA-P in plasma. Interestingly, the expression levels of hsa-miR-19b-3p and hsa-miR-24-3p were positively correlated, indicating that these miRNAs may be involved in the same processes in PD pathogenesis. Our findings suggest that hsa-miR-671-5p, hsa-miR-19b-3p, and hsa-miR-24-3p may reflect the pathophysiology or symptoms of PD and MSA.
Highlights
Multiple system atrophy (MSA) is an adult-onset progressive neurodegenerative disorder that is clinically characterized by autonomic dysfunction, cerebellar ataxia, poorly L-dopa-responsive parkinsonism, and pyramidal dysfunction
Patients and sample collection Healthy controls and patients with probable MSA-C, probable MSA-P, and Parkinson’s disease (PD) who were diagnosed at Hokkaido University Hospital, Obihiro Kosei General Hospital, and Kushiro Rosai Hospital were enrolled in this study
Using microarray analysis, we screened for plasma miRNAs that were differentially expressed in patients with MSA and in healthy controls and performed qPCR to quantitatively analyze the top four up-regulated and seven down-regulated miRNAs
Summary
Multiple system atrophy (MSA) is an adult-onset progressive neurodegenerative disorder that is clinically characterized by autonomic dysfunction, cerebellar ataxia, poorly L-dopa-responsive parkinsonism, and pyramidal dysfunction. Pathological features include the presence of glial cytoplasmic inclusions (GCIs) in oligodendroglia that contains misfolded a-synuclein, neuronal loss, astroglial. Parkinson’s disease (PD) is the second most frequent chronic neurodegenerative disorder and is clinically characterized by motor and nonmotor symptoms. The crucial pathological features of PD are the loss of dopaminergic neurons within the substantia nigra pars compacta [5] and the deposition of α-synuclein, which aggregates in a misfolded state and forms intracellular inclusions within the cell body (Lewy bodies) and processes (Lewy neurites) of neurons [6]. MSA and PD are both categorized as α-synucleinopathies and, at the early stage of the disease, often present similar clinical manifestations, which often makes precise differentiation and diagnosis of these conditions difficult. The identification of disease biomarkers that can differentiate MSA and PD is strongly desired
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