Xue Zhang,1,2 Li Xue,3 Haiyan Li,2 Xiaolong Yu,2 Kaixin Dou,1 Anmu Xie1 

1Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Neurology, Qingdao Central Hospital, University of Health and Rehabilitation Sciences, Qingdao, People’s Republic of China; 3Department of Internal Medicine, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China

Correspondence: Anmu Xie, Department of Neurology, Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Tel +86 532 82912336, Fax +8653282911999, Email xieanmu@163.com

Background: The aim was to investigate the potential role of TP73-AS1 in the pathogenesis of Parkinson’s disease.
Methods: Peripheral blood samples were obtained from three patients with early-onset Parkinson’s disease (PD), three patients with late-onset PD, and three healthy controls for the extraction of total RNA. Genomic long non-coding RNA (lncRNA) expression levels were analyzed using the Illumina HiSeq2500 sequencing platform. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to study the expression of TP73-AS1. Flow cytometry and Western blot analyses were conducted to assess the functional role of TP73-AS1 in SH-SY5Y cells in vitro. Moreover, the expression of inflammatory cytokines, such as IL-16, IL-6, and α-synuclein (SYN), was examined using cellular immunofluorescence techniques.
Results: Among early-onset PD patients, 59 lncRNAs were significantly upregulated, and 57 lncRNAs were significantly downregulated compared to the control group. Similarly, late-onset PD patients showed 70 upregulated lncRNAs and 77 downregulated lncRNAs with statistical significance compared to the control group. In vitro studies indicated a significant increase in lncRNA TP73-AS1 expression in the MPP+-treated group in contrast with the control group (P < 0.001). Furthermore, the MPP+-treated group displayed elevated levels of Cleaved caspase-3, IL-16, as well as IL-6 (P < 0.001). Conversely, Bcl-2 expression decreased, Bax expression increased, and the Bax/Bcl-2 expression ratio demonstrated an increase (P < 0.001). Reducing lncRNA TP73-AS1 resulted in decreased apoptosis and inflammation, along with a decrease in α-SYN expression (P < 0.001). Notably, the absence of TP73-AS1 showed a protective effect against PD, suggesting it to be a potential target for the treatment of PD. These findings suggest that TP73-AS1 may serve as a potential molecular marker for the early diagnosis of PD, providing a new perspective for understanding the regulatory mechanisms of inflammation and apoptosis in PD.

Keywords: TP73-AS1, long non-coding RNA, apoptosis, inflammation, high-throughput sequencing