Abstract
Serum miR-30c-5p correlates with Parkinson’s disease (PD), yet its role has not been illustrated. This research analyzed the function of miR-30c-5p in PD. The behavioral evaluation was performed on MPTP-treated PD mice transfected with miR-30c-5p agomiR, antagomiR, siATG5, or 3-MA (an autophagy inhibitor). Oxidative stress-related factors, miR-30c-5p, and apoptosis- and autophagy-associated proteins in brain tissues or cells were determined by molecular experiments. Tyrosine hydroxylase (TH) and dopamine metabolic markers were detected using immunofluorescence and Diode Array Detector (DAD), respectively. Effects of miR-30c-5p and its target gene Autophagy-related gene (ATG) 5 protein (ATG5) on MPP+-treated SH-SY5Y cells were determined through a series of molecular experiments. MiR-30c-5p was upregulated but ATG5 was downregulated in PD mice. MiR-30c-5p antagomiR attenuated the decrease of ATG5 in PD mice. MiR-30c-5p antagomiR partly alleviated the behavioral symptoms and inhibited the increases of malondialdehyde (MDA), catalase (CAT), and SOD in PD mice. The levels of Bcl-2, dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), TH, and LC3 II were downregulated in PD mice, while Bax, cleaved caspase-3, P62, and LC3 I were upregulated. However, miR-30c-5p antagomiR partly reversed the levels of these factors in PD mice. 3-MA could block the effects of miR-30c-5p antagomiR on PD mice. MiR-30c-5p antagomiR attenuated apoptosis and induced autophagy in brain tissues of MPTP-treated mice by targeting ATG5. In vitro assay results also showed that silence of ATG5 reduced the protective effect of miR-30c-5p downregulation on the cells. MiR-30c-5p regulates the progression of Parkinson’s disease through attenuating ATG5-inhibited apoptosis and -induced autophagy.
Highlights
Parkinson’s disease is a common age-related neurodegenerative disease mainly manifested by the loss of dopaminergic (DA) neurons in the substantia nigra (SN), and the accumulation of α-synuclein (α-syn) in the cytoplasm of neurons or glial cells (Lancet, 2017)
We found that autophagy-related gene 5 protein (ATG5) level was decreased in the Mmodel group compared to the control group, which was further promoted by siATG5 treatment; by contrast, miR-30c-5p downregulation abrogated the inhibitive effect of siATG5 on ATG5 expression in model mice (Figure 8A; p < 0.001)
We discovered a link between miR-30c-5p and ATG5, and that miR-30c-5p aggravated neuronal damage via negatively regulating ATG5 expression and decreasing autophagy levels in the Parkinson’s disease (PD) mice and cell model
Summary
Parkinson’s disease is a common age-related neurodegenerative disease mainly manifested by the loss of dopaminergic (DA) neurons in the substantia nigra (SN), and the accumulation of α-synuclein (α-syn) in the cytoplasm of neurons or glial cells (Lancet, 2017). The accumulation of α-syn in the neuropathological hallmark of Lewy bodies could induce the death of dopaminergic neurons (Ayers et al, 2018). The Lewy bodies will be degraded in dopaminergic cells, but in PD, dopaminergic cells are deficient in the degradation of damaged or abnormally modified proteins (Ebrahimi-Fakhari et al, 2012). Evidence suggested that dysregulation of miRNAs occurs in neurodegenerative diseases. About 70% of miRNAs are expressed and regulated in the key signaling pathways in brain development (Nadim et al, 2017). MiR-30c-5p may serve as a biomarker to improve the clinical diagnosis or prognosis prediction in patients with PD, and a potential therapeutic target for the treatment of PD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
