A Transcriptome Analysis of mRNAs and Long Non-Coding RNAs in Patients with Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The number of cases of PD is expected to double by 2030, representing a heavy burden on the healthcare system. Clinical symptoms include the progressive loss of dopaminergic neurons in the substantia nigra of the midbrain, which leads to striatal dopamine deficiency and, subsequently, causes motor dysfunction. Certainly, the study of the transcriptome of the various RNAs plays a crucial role in the study of this neurodegenerative disease. In fact, the aim of this study was to evaluate the transcriptome in a cohort of subjects with PD compared with a control cohort. In particular we focused on mRNAs and long non-coding RNAs (lncRNA), using the Illumina NextSeq 550 DX System. Differential expression analysis revealed 716 transcripts with padj ≤ 0.05; among these, 630 were mRNA (coding protein), lncRNA, and MT_tRNA. Ingenuity pathway analysis (IPA, Qiagen) was used to perform the functional and pathway analysis. The highest statistically significant pathways were: IL-15 signaling, B cell receptor signaling, systemic lupus erythematosus in B cell signaling pathway, communication between innate and adaptive immune cells, and melatonin degradation II. Our findings further reinforce the important roles of mitochondria and lncRNA in PD and, in parallel, further support the concept of inverse comorbidity between PD and some cancers.

Comprehensive Analysis Identifies Ameloblastin-Related Competitive Endogenous RNA as a Prognostic Biomarker for Testicular Germ Cell Tumour

“…A valid regulatory pathway, LINC02701-hsa-miR-3153-GFAP, was identified based on subcellular localisation and sequence alignment validation. LINC02701 has not been previously reported to be associated with cancer, but LINC02701 mRNA expression was significantly raised in patients with Parkinson's disease compared to normal controls [62]. Additionally, LINC02701 was analysed in the recent SARS-CoV-2 study as being associated with the antiviral function of cells and involved in the coordinated expression of signalling pathways in the immune response [63].…”

Type I Diabetes Pathoetiology and Pathophysiology: Roles of the Gut Microbiome, Pancreatic Cellular Interactions, and the ‘Bystander’ Activation of Memory CD8+ T Cells

“…In Parkinson’s disease models, the induction of mitochondrial oxidative stress enhances MHC-1, which then increases the attraction of CD8 + T cells to the substantia nigra [ 143 ]. The mitochondrial melatonergic pathway is suppressed in the substantia nigra in Parkinson’s disease [ 67 , 144 ], indicating a relevant role for mitochondrial melatonergic pathway suppression in the pathophysiology of immune-mediated, classical ‘autoimmune’ disorders more widely. In Parkinson’s disease models, suppressed mitochondrial PTEN-induced kinase 1 (PINK1) is proposed to contribute to, if not underpin, MHC-1 upregulation [ 143 ], coupled to a decrease in mitophagy and associated metabolic dysregulation.…”

Examples of Inverse Comorbidity between Cancer and Neurodegenerative Diseases: A Possible Role for Noncoding RNA

“…LINC00487 is a lncRNA that has been shown to be downregulated in a transcriptome study of PD subjects [ 94 ]. On the other hand, LINC00487 was found to be upregulated in squamous cell carcinoma of the lungs [ 175 ].…”

“…It is upregulated in myocardial infarction [ 90 ], exerts a protective role in ischemic stroke [ 91 ] and also participates in PD, where it increases the stability of α-synuclein [ 92 ]. Therefore, accumulating evidence demonstrates that long-noncoding RNAs (lncRNAs) may affect the pathogenesis of several diseases, especially cancers and neuroimmunological and neurodegenerative disorders [ 93 , 94 , 95 , 96 ].…”