Abstract
Objective: To investigate the expression level of the maternally expressed gene-3 (MEG3) of the free long non-coding RNA (lncRNAs) in the plasma of Parkinson's disease (PD) patients and its relationship with the disease.Methods: Thirty PD patients (PD group) who treated at Xuanwu Hospital of Capital University of Medical Sciences between January 2017 and December 2019 were selected as the research objects and 30 healthy subjects were enrolled in the study during the same period as the control group. Cognitive function was assessed according to the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function, Non-Motor Symptoms Scale (NMSS) was used to evaluate severity of non-motor symptoms. The relative expression of lncRNAs MEG3 in plasma was measured by PCR, and the levels of neuron-specific enolase (NSE), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in plasma were measured by ELISA, and the relationship with these all indexes was analyzed.Results: The NMSS score of PD group was significantly higher than that of the control group, while the MMSE and MoCA scores were significantly lower than that of the control group (P < 0.05); The relative expression of lncRNAs MEG3, NGF and BDNF levels of PD group were significantly lower than that of the control group, and NSE level was significantly higher than that of the control group (P < 0.05); The H&Y stage and NMSS score in PD group were negatively correlated with the relative expression of lncRNAs MEG3, the levels of NGF and BDNF (P < 0.05), and positively correlated with NSE (P < 0.05); The MMSE and MoCA scores in PD group were positively correlated with the relative expression of lncRNAs MEG3, NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05); The relative expression of lncRNAs MEG3 in PD group was positively correlated with NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05).Conclusion: The expression of lncRNAs MEG3 in the plasma of PD patients was downregulated compared to that of healthy control subjects, and its expression level was closely related to the aggravation of non-motor symptoms, cognitive decline, and PD stage. These associations may reflect the synergism of the increase of NSE and decrease of NGF and BDNF levels, highlighting plasma lncRNA MEG3 as a new candidate biomarker of PD.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disease and the second most common neurodegenerative disease worldwide, following Alzheimer’s disease, affecting 2–3% of the global population ≥65 years of age, and the incidence rate has been increasing steadily every year [1, 2]
Plasma long non-coding RNAs (lncRNAs) maternally expressed gene-3 (MEG3) levels were negatively correlated with neuron-specific enolase (NSE) levels in PD patients (r = −0.181, P = 0.019), and positively correlated with nerve growth factor (NGF) (r = 0.131, P = 0.049) and brain-derived neurotrophic factor (BDNF) (r = 0.351, P = 0.001) levels
The results showed that age, disease course, Non-Motor Symptoms Scale (NMSS) and NSE was significantly positively correlated with disease stage, while Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) scores and the relative expression of lncRNA MEG3 levels were significant negatively correlated with disease stage, and the differences were statistically significant (P < 0.05) (Table 4)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease and the second most common neurodegenerative disease worldwide, following Alzheimer’s disease, affecting 2–3% of the global population ≥65 years of age, and the incidence rate has been increasing steadily every year [1, 2]. The number of PD patients in China was estimated at about 5 million in 2019, accounting for half of the world’s total number of cases, affecting quality of life for the patients and imposing an economic burden on society [3]. With non-motor symptoms, other symptoms appear such as REM sleep behavior disorders (or RBD), olfactory dysfunction, constipation, pain, fatigue, sleep disorders, autonomic dysfunction, and cognitive dysfunction that seriously affect the quality of life of patients; in particular, the incidence of cognitive dysfunction reaches 80% or more among patients with PD [4,5,6]. The central link of these mechanisms involves a multi-molecular pathway network, and synergistic effects induce the degeneration of dopaminergic neurons [8]. Mining early biomarkers is of great significance for the diagnosis, treatment, and prognosis of PD
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