Abstract
Levodopa-induced dyskinesia (LID) is a common complication of chronic dopamine replacement therapy in the treatment of Parkinson’s disease (PD). Long noncoding RNAs regulate gene expression and participate in many biological processes. However, the role of long noncoding RNAs in LID is not well understood. In the present study, we examined the lncRNA transcriptome profile of a rat model of PD and LID by RNA sequence and got a subset of lncRNAs, which were gradually decreased during the development of PD and LID. We further identified a previously uncharacterized long noncoding RNA, NONRATT023402.2, and its target genes glutathione S-transferase omega (Gsto)2 and prostaglandin E receptor (Ptger)3. All of them were decreased in the PD and LID rats as shown by quantitative real-time PCR, fluorescence in situ hybridization and western blotting. Pearson’s correlation analysis showed that their expression was positively correlated with the dyskinesia score of LID rats. In vitro experiments by small interfering RNA confirmed that slicing NONRATT023402 inhibited Gsto2 and Ptger3 and promoted the inflammatory response. These results demonstrate that NONRATT023402.2 may have inhibitive effects on the development of PD and LID.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and affects approximately 7 million people—mostly elderly—worldwide [1]
Immunohistochemical detection of tyrosine hydroxylase (TH), a marker of dopaminergic neurons [24], showed that striatal 6-OHDA injections resulted in a dramatic loss of dopaminergic neuron in the substantia nigra (SN) and dopaminergic neuron degeneration in the striatum of PD, L-DOPA-induced dyskinesia (LID), and NLID rats on the side ipsilateral to the injection site (Figure 1C)
There was a slight increase in TH levels in the striatum of LID and NLID rats that were administered L-DOPA for 3 weeks compared with PD rats (Figure 1D), suggesting that L-DOPA prevents the loss of dopaminergic neurons
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, and affects approximately 7 million people—mostly elderly—worldwide [1]. PD is characterized by motor symptoms, massive and selective loss of dopaminergic neurons in the substantia nigra (SN), and a decrease in striatal dopamine concentration [2] and is caused by genetic and non-genetic factors [3, 4]. Dopamine replacement therapy with the dopamine precursor. Levodopa (L-DOPA) is the most effective symptomatic treatment for PD. L-DOPA can significantly improve PD symptoms, long-term use typically leads to the gradual development of hyperkinetic involuntary movements known as L-DOPA-induced dyskinesia (LID), which manifests as nonrhythmic, nondirected involuntary movements that are unpredictable in onset and severity. LID is observed in nearly 90% of PD patients within approximately 10 years of initiating LDOPA therapy [5]. The molecular basis for LID are not fully understood; clarifying the molecular www.aging-us.com mechanisms is essential to identifying new therapeutic targets for its treatment [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
