MicroRNA as diagnostic biomarker in Parkinson’s Disease.

An estimated prevalence of 1% of people above 60 years old suffer from Parkinson’s disease (PD). PD mainly involves a progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc), which resulting in the corresponding decrease in dopamine neurotransmitter signaling and manifest as motor dysfunctions and clinical symptoms such as resting tremor, bradykinesia, rigidity and postural instability. In addition, Lewy bodies which are enriched with the intracellular inclusion of α-synuclein protein (α-syn) in the neurons of PD patients, are suggested to impair pathways such as vesicle trafficking or activating neuroinflammation (Goh et al., 2019).
The diagnosis of PD is still based on the assessment of clinical criteria mentioned above, which leads to an insufficient diagnostic accuracy. No definitive biomarker so far is available allowing the prediction or diagnosis of the disease course or monitoring the response to therapeutic approaches. Over the past decade, with techniques such as RNA sequencing, microarray and microRNA qPCR profiling, screening studies have been conducted to report that miRNAs expression profile is altered not just in brain tissues, and also peripheral body fluid such as cerebral spinal fluid, blood, or even saliva and urine. miRNAs in periphery might be the promising diagnostic candidates for PD, as they are easily accessible by non- or minimally-invasive procedures and changes in their expression are associated with pathophysiological processes relevant for PD (Roser et al., 2019).

miRNA in blood
Blood and its derivatives are the most extensively studied source fluid. Analysis of miRNA levels in whole blood by PCR arrays revealed a set of differentially expressed miRNAs that permitted the discrimination of PD patients and controls (miR-1-3p, miR-22-5p, and miR-29a-3p), as well as differentiating between Levodopa/Carbidopa-treated and untreated PD groups (miR-16-2-3p, miR-26a-2-3p, and miR30a-5p) (Margis et al., 2011). miR-137-3p and miR-124-3p were found significantly regulated in the serum from PD patients (Li et al., 2017). Ravanidis et al. reported the miRNAs profiling in serum were different between idiopathic and genetic PD, but were very similar between the genetic forms of PD. miR-132-3p (P = 0.083) and hsa-miR-433-3p were significantly upregulated, whereas miR-128-3p (P = 0.01), miR-136-3p, miR-154-5p, miR-323a-3p, (P = 0.055), miR-382-5p, miR-409-3p, miR-410-3p, and miR-485-5p, were significantly downregulated in both the GBA and SNCA mutations PD patients. This suggested that both mutations converge on the same master miRNAs that drive the pathophysiological process in PD.

miRNA in peripheral blood mononuclear cell (PMBC)
Microarray analysis of 19 PD and 13 control cases identified 18 miRNAs altered in PD, including several of the regulated miRNAs found in serum/plasma, miR-335, miR-374a, miR-199a-3p, miR-199b-3p, miR-126, miR-151-3p, miR-151-5p, miR-29b, miR-147, miR-28-5p, miR-30b, miR-374b, miR-19b, miR-30c, miR-29c, miR-301a, miR-26 (Martins et al., 2011). Then, RT-qPCR analysis revealed increased expression of miR-103a-3p, miR-30b-5p, and miR-29a-3p in PBMCs of PD patients (Serafin et al., 2015)

miRNA in cerebrospinal fluid (CSF)
Burgos et al. reporting that the miRNA signature in CSF seems to be slightly more stable (Burgos et al., 2014). The level of miR-132-5p in CSF was observed decreased in PD (Gillardon et al., 2008). Quantitative RT-PCR analysis of 44 PD and 42 controls
identified miR-200a-3p, miR-542-3p, and miR-144-5p upregulated in CSF of PD patients. And these candidates showed a high correlation with disease stages (Mo et al., 2016). Exosome miRNAs isolated from CSF also show differential expression according to disease states. Studies investigating such type of sample revealed miR-1, miR-19b-3p decreased expression in PD, while miR-153, miR-409-3p, miR-10a-5p, and let-7g-3p were found upregulated.

miRNA in saliva
The finding of miRNA in saliva is followed on from the previous work studying the overexpression of haem oxygenase 1 (HO1) in PD. The team led by Hyman Schipper previously found significant elevation of HO1 protein in the saliva of patients with PD so then they further investigated the downstream miRNA of HO1 pathway. They collected saliva from 83 patients with PD and 77 controls with no neurological condition. The samples were analyzed with RT-qPCR to measure levels of miR-153 and miR-223. Salivary levels of both miRNAs were lower in patients with PD than in controls (Cressatti et al. 2019).
Already, numerous studies have revealed a number of miRNAs in periphery as potential biomarkers for PD and other Parkinsonian syndromes. However, the overlap among the candidates is low in different studies, and the changes of miRNA in stages of the pathological progression needs to gather more findings. Additionally, fast, reliable, easy-to-handle, and cost-efficient miRNA detection methods are needed to further develop miRNAs as diagnostic biomarker for clinical use.
TOOLS launched a comprehensive list of miRNA assays that covers miRNAs reported in PD studies. The TOOLS miRNA assay system consists of TOOLS miRNA RT Kit, TOOLS miRNA RT-qPCR primer/probe set, and TOOLS Easy 2X probe qPCR mix. All TOOLS miRNA RT-qPCR primer/probe set are pre-designed, well-validated and QC. Customized design and production of miRNA RT-qPCR primer/probe set is also available. TOOLS miRNA assay allows rapid, sensitive, and specific profiling the expression of microRNA (miRNA) within the simple 2-step RT-qPCR procedure. To see the full list of TOOLS miRNA assay and related products, please click TOOLS Life Science Reagents -‎.

TOOLS provides well-validated RT-qPCR assay set to PD associated miRNAs.
Product name miRNA ACC Product name miRNA ACC Product name miRNA ACC Product name miRNA ACC
cel-miR-39-3p MIMAT0000424 hsa-miR-133a-3p MIMAT0000086 hsa-miR-193a-5p MIMAT0000770 hsa-miR-34a-5p MIMAT0000682
cel-miR-54-3p MIMAT0000434 hsa-mir-133a-5p MIMAT0000088 hsa-miR-193b-3p MIMAT0000451 hsa-miR-3615 MIMAT0004694
hsa-let-7a-5p MIMAT0000433 hsa-miR-133b MIMAT0000692 hsa-miR-194-5p MIMAT0000232 hsa-miR-365a-3p MIMAT0004585
hsa-let-7b-5p MIMAT0000435 hsa-miR-135a-5p MIMAT0000763 hsa-miR-196a-5p MIMAT0000510 hsa-miR-3688-3p MIMAT0004762
hsa-let-7d-3p MIMAT0000437 hsa-miR-135b-5p MIMAT0000441 hsa-miR-197-3p MIMAT0004748 hsa-miR-374b-5p MIMAT0019856
hsa-let-7d-5p MIMAT0000257 hsa-miR-139-3p MIMAT0000092 hsa-miR-199a-3p MIMAT0002816 hsa-miR-4488 MIMAT0031177
hsa-let-7g-5p MIMAT0000440 hsa-miR-1-3p MIMAT0000093 hsa-miR-19a-3p MIMAT0000063 hsa-miR-450a-5p MIMAT0000442
hsa-miR-100-5p MIMAT0000461 hsa-miR-140-3p MIMAT0004600 hsa-miR-200a-3p MIMAT0003303 hsa-miR-4755-3p MIMAT0003150
hsa-miR-101-3p MIMAT0000271 hsa-miR-141-3p MIMAT0000253 hsa-miR-200c-3p MIMAT0005881 hsa-miR-4793-3p MIMAT0000420
hsa-miR-101-5p MIMAT0000280 hsa-miR-142-3p MIMAT0000254 hsa-miR-203a-3p MIMAT0000067 hsa-miR-486-3p MIMAT0000454
hsa-miR-103a-3p MIMAT0004570 hsa-miR-142-5p MIMAT0000428 hsa-mir-204-3p MIMAT0004597 hsa-miR-499a-5p MIMAT0000083
hsa-miR-106a-5p MIMAT0002820 hsa-miR-143-3p MIMAT0000758 hsa-miR-204-5p MIMAT0000265 hsa-miR-500a-3p MIMAT0000269
hsa-miR-106b-3p MIMAT0004916 hsa-miR-144-3p MIMAT0000256 hsa-miR-20a-5p MIMAT0002888 hsa-miR-501-3p MIMAT0000444
hsa-miR-107 MIMAT0000098 hsa-miR-144-5p MIMAT0000073 hsa-miR-211-5p MIMAT0000446 hsa-miR-502-3p MIMAT0000426
hsa-miR-10a-3p MIMAT0000101 hsa-miR-145-5p MIMAT0000074 hsa-miR-215-5p MIMAT0000259 hsa-miR-506-3p MIMAT0000693
hsa-miR-10b-3p MIMAT0000680 hsa-miR-146a-5p MIMAT0000243 hsa-miR-221-3p MIMAT0000082 hsa-miR-509-5p MIMAT0003880
hsa-miR-1180-3p MIMAT0000443 hsa-miR-148a-3p MIMAT0000759 hsa-miR-223-3p MIMAT0004515 hsa-miR-548f-5p MIMAT0001340
hsa-miR-1229-3p MIMAT0000068 hsa-miR-148a-5p MIMAT0005898 hsa-miR-223-5p MIMAT0000087 hsa-miR-550a-5p MIMAT0003283
hsa-miR-1238-3p MIMAT0000417 hsa-miR-151a-3p MIMAT0000423 hsa-miR-224-5p MIMAT0006764 hsa-miR-576-5p MIMAT0000065
hsa-miR-1246 MIMAT0000069 hsa-miR-15a-5p MIMAT0000449 hsa-miR-22-5p MIMAT0000753 hsa-miR-615-3p MIMAT0004703
hsa-miR-1247-5p MIMAT0000070 hsa-miR-15b-5p MIMAT0002819 hsa-miR-26a-1-3p MIMAT0002880 hsa-miR-624-3p MIMAT0004955
hsa-miR-125a-5p MIMAT0000261 hsa-miR-16-5p MIMAT0004767 hsa-miR-27b-3p MIMAT0003218 hsa-miR-625-3p MIMAT0004784
hsa-miR-126-3p MIMAT0000072 hsa-miR-17-5p MIMAT0000077 hsa-miR-29a-3p MIMAT0000226 hsa-miR-629-5p MIMAT0015083
hsa-miR-126-5p MIMAT0001080 hsa-miR-181a-3p MIMAT0000078 hsa-miR-29a-5p MIMAT0000455 hsa-miR-633 MIMAT0001536
hsa-miR-127-3p MIMAT0000617 hsa-miR-181a-5p MIMAT0000255 hsa-miR-30a-3p MIMAT0003393 hsa-miR-664a-3p MIMAT0000757
hsa-miR-1276 MIMAT0000264 hsa-miR-181b-5p MIMAT0003339 hsa-miR-30a-5p MIMAT0004807 hsa-miR-671-5p MIMAT0019206
hsa-miR-128-3p MIMAT0000266 hsa-miR-183-5p MIMAT0000414 hsa-miR-30b-5p MIMAT0005577 hsa-miR-744-5p MIMAT0000686
hsa-miR-1291 MIMAT0000076 hsa-miR-184 MIMAT0000275 hsa-miR-3158-3p MIMAT0004949 hsa-miR-7706 MIMAT0000710
hsa-miR-1307-5p MIMAT0000278 hsa-miR-185-5p MIMAT0000416 hsa-miR-324-3p MIMAT0005953 hsa-miR-92a-3p MIMAT0001412
hsa-miR-130b-3p MIMAT0000279 hsa-miR-187-3p MIMAT0000084 hsa-miR-330-3p MIMAT0003945 hsa-miR-92b-3p MIMAT0000762
hsa-miR-130b-5p MIMAT0000080 hsa-miR-18a-5p MIMAT0000419 hsa-miR-339-3p MIMAT0022693 hsa-miR-937-3p MIMAT0004495
hsa-miR-1322 MIMAT0000081 hsa-miR-18b-5p MIMAT0000100 hsa-miR-340-5p MIMAT0001639 hsa-miR-9-3p MIMAT0000765
hsa-miR-132-3p MIMAT0004498 hsa-miR-1909-3p MIMAT0000244 hsa-miR-342-5p MIMAT0004681 SNORD48 MIMAT0004503


  • Burgos K, Malenica I, Metpally R, Courtright A, Rakela B, Beach T, Shill H, Adler C, Sabbagh M, Villa S, Tembe W, Craig D, Van Keuren-Jensen K. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology. PLoS One. 2014 May 5;9(5):e94839. doi: 10.1371/journal.pone.0094839.
  • Cressatti M, Juwara L, Galindez JM, Velly AM, Nkurunziza ES, Marier S, Canie O, Gornistky M, Schipper HM. Salivary microR-153 and microR-223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease. Mov Disord. 2020 Mar;35(3):468-477. doi: 10.1002/mds.27935.
  • Gillardon F, Mack M, Rist W, Schnack C, Lenter M, Hildebrandt T, Hengerer B. MicroRNA and proteome expression profiling in early-symptomatic α-synuclein(A30P)-transgenic mice. Proteomics Clin Appl. 2008 May;2(5):697-705. doi: 10.1002/prca.200780025.
  • Goh SY, Chao YX, Dheen ST, Tan EK, Tay SS. Role of MicroRNAs in Parkinson's Disease. Int J Mol Sci. 2019 Nov 12;20(22):5649. doi: 10.3390/ijms20225649.
  • Li N, Pan X, Zhang J, Ma A, Yang S, Ma J. Plasma levels of miR-137 and miR-124 are associated with Parkinson’s disease but not with Parkinson’s disease with depression. Neurol. Sci. 2017, 38, 761–767. doi: 10.1007/s10072-017-2841-9
  • Margis R and Rieder CRM. Identification of blood microRNAs associated to Parkinsonós disease. J. Biotechnol. 2011, 152, 96–101. doi: 10.1016/j.jbiotec.2011.01.023
  • Martins, M., Rosa, A., Guedes, L. C., Fonseca, B. V., Gotovac, K., Violante, S. Convergence of miRNA expression profiling, a-synuclein interacton and GWAS in Parkinson’s disease. PLoS One 2011, 6:e25443. doi: 10.1371/journal. pone.0025443
  • Mo M, Xiao Y, Huang S, Cen L, Chen X, Zhang L, Luo Q, Li S, Yang X, Lin X, Xu P. MicroRNA expressing profiles in A53T mutant alpha-synuclein transgenic mice and Parkinsonian. Oncotarget. 2017 Jan 3;8(1):15-28. doi: 10.18632/oncotarget.13905.
  • Ravanidis S, Bougea A, Papagiannakis N, Maniati M, Koros C, Simitsi AM, Bozi M, Pachi I, Stamelou M, Paraskevas GP, Kapaki E, Moraitou M, Michelakakis H, Stefanis L, Doxakis E. Circulating Brain-enriched MicroRNAs for detection and discrimination of idiopathic and genetic Parkinson's disease. Mov Disord. 2020 Mar;35(3):457-467. doi: 10.1002/mds.27928.
  • Roser AE, Caldi Gomes L, Schünemann J, Maass F, Lingor P. Circulating miRNAs as Diagnostic Biomarkers for Parkinson's Disease. Front Neurosci. 2018 Sep 5;12:625. doi: 10.3389/fnins.2018.00625.
  • Serafin A, Foco L, Zanigni S, Blankenburg H, Picard A, Zanon A, Giannini G, Pichler I, Facheris MF, Cortelli P, Pramstaller PP, Hicks AA, Domingues FS, Schwienbacher C. Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD. Neurology. 2015 Feb 17;84(7):645-53. doi: 10.1212/WNL.0000000000001258.
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