Circulating miRNAs as Biomarkers for Neurodegenerative Disorders
Abstract
:1. Introduction
1.1. miRNA Biogenesis and Functions
1.2. miRNAs in the Nervous System
2. Neurodegenerative Diseases
2.1. Biomarkers in Neurodegenerative Diseases
2.2. Circulating microRNAs as Biomarkers for Neurodegenerative Diseases
2.2.1. Alzheimer’s Disease and Circulating miRNAs
2.2.2. Parkinson’s Disease and Circulating miRNAs
2.2.3. Amyotrophic Lateral Sclerosis and Circulating miRNAs
miRNA | Sample | Experimental approach | Pilot study | Validation study | Reference |
---|---|---|---|---|---|
Increased expression of miR-34a and miR-181b | PBMC | miRNA profiling | Microarray
AD: 16 NEC: 16 | Taqman® miRNA qRT-PCR | [41] |
12-miRNA signature: miR-112, miR-161, let-7d-3p, miR-5010-3p, hsa-miR-26a-5p, hsa-miR-1285-5p, and hsa-miR-151a-3p upregulated; miR-103a-3p, miR-107, miR-532-5p, miR-26b-5p, let-7f-5p downregulated | Peripheral blood | miRNA profiling | Next Generation Sequencing
AD: 48 CT: 22 | SYBR qRT-PCR
AD: 94 MCI: 18 MS: 16 PD: 9 DEP: 15 BD: 15 Schiz: 14 CT: 21 | [42] |
7-miRNA signature: hsa-let-7d-5p, hsa-let-7g-5p, hsa-miR-15b-5p, hsa-miR-142-3p, hsamiR-191-5p, hsa-miR-301a-3p and hsa-miR-545-3p | Plasma | miRNA profiling | Nanostring
AD: 11 MCI: 9 CT: 20 | Taqman® miRNA qRT-PCR AD: 20 CT: 17 | [43] |
Reduced expression of miR-27a-3p | CSF | miRNA profiling | qRT-PCR
AD CT | qRT-PCR
AD: 35 CT: 37 | [44] |
60 miRNAs differentially regulated between the different Braak stages, including Let-7 family members | CSF | miRNA profiling | Taqman® miRNA qRT-PCR Braak stage V AD: 10 Braak stage I non demented controls: 10 | [45] | |
Elevated levels of miR-146a and miR-155 | CSF and ECF | Candidate miRNAs | Microarray
AD: 5 CT: 5 | [47] | |
Significant increase in miR-9, miR-125b, miR-146a, miR-155 | CSF and ECF | Candidate miRNAs | Microarray
AD: 6 CT: 6 | [46] | |
Elevated levels of let-7b | CSF | Candidate miRNAs | Taqman® miRNA qRT-PCR AD: 13 CT: 11 | [48] | |
miR-15a associated with amyloid plaque score | Plasma | Candidate miRNAs | Microarray | qRT-PCR | [49] |
miR-29a/b, miR-181c, and miR-9 down-regulated | Serum | Candidate miRNAs | SYBR qRT-PCR
AD: 7 MCI/Early AD: 7 CT: 7 | [50] | |
Increased levels of miR-34c | PBMC or cell-free plasma | Candidate miRNAs | Taqman® miRNA qRT-PCR AD: 110 CT: 123 | [51] | |
Circulating brain-enriched miRNAs: “miR‐132 family” and “miR‐134 family” | Plasma | Candidate miRNAs | TaqMan® miRNA qRT-PCR MCI: 10 CT: 10 | TaqMan® qRT-PCR MCI: 20 AD: 20 CT: 20 CY: 20 | [53] |
miRNA | Sample | Experimental approach | Pilot study | Validation study | Reference |
---|---|---|---|---|---|
18 significantly under-expressed miRNAs | PBMC | miRNA profiling | Microarray PD: 19 CT: 13 | [57] | |
miR-1, miR-22-5p and miR-29 distinguish non-treated PD from healthy subjects | Total peripheral blood | miRNA profiling | qRT-PCR untreated PD: 8 treated PD: 4 early-onset PD: 7 CT: 8 | [58] | |
miR-16-2-3p, miR-26a-2-3p, miR30a differentiate treated from untreated patients | Total peripheral blood | miRNA profiling | qRT-PCR untreated PD: 8 treated PD: 4 early-onset PD: 7 CT: 8 | [58] | |
miR-331-5p upregulated | Plasma | miRNA profiling | Taqman® miRNA qRT-PCR PD: 31 CT: 25 | [59] | |
miR-1826, miR-450b-3p, miR-626, and miR-505 | Plasma | miRNA profiling | Agilent microarray PD: 32 CT: 32 | Taqman® miRNA qRT-PCR treated PD: 20 untreated PD: 10 PSP: 5 MSA: 4 CT: 4 | [60] |
16 miRNAs (including miR-16, miR-20a and miR-320) modified in patients pre-DBS | Leukocytes | miRNA profiling | Next Generation Sequencing PD pre-DBS: 3 PD post-DBS: 3 CT: 6 | [61] |
miRNA | Sample | Experimental approach | Pilot study | Validation study | Reference |
---|---|---|---|---|---|
8 miRNAs (miR-451, miR-1275, miR-328, miR-638, miR-149, miR-665 and miR-338-3) significantly up- or downregulated | Leukocytes | miRNA profiling | Microarray ALS: 8 CT: 12 | TaqMan® miRNA qRT-PCR ALS: 14 CT: 14 | [64] |
Expression of ALS-specific miRNA inflammatory signature | Monocytes | miRNA profiling | Microarray
ALS: 8 MS: 8 CT: 8 | [65] |
3. Neurodegenerative Diseases Meet Cancers in a miRNA World
miRNA | Target genes | Expression in cancer | Expression in neurodegenerative disorders | Reference |
---|---|---|---|---|
let-7 family, miR-17-5p, miR-20a miR-106b | APP | Oncogene, over-expressed in oral cavity, esophageal, pancreatic, neuroendocrine, thyroid, and colorectal cancer | Concentrated at neuronal synapses and in AD-associated amyloid plaques | [69,70,71,72,73,74,75,76] |
miR-29a/b-1 family | BACE1 | Decrease of ST6GalI-mediated cancer cell migration | High expression in patients with sporadic AD | [78,79] |
miR-21 miR-106b | PTEN | Tumour suppressor, mutated in sporadic and inherited tumours | Implicated in PD through activation of PINK1 and PARK7 | [80,81,82] |
miR-34b/c | PARK2 | Tumour suppressor, mutated in glioblastoma, lung cancer and colon cancer | Reduced in PD brain samples displaying strong miR-34b/c downregulation | [67,83] |
miRNA | Disease | Target genes | Reference |
---|---|---|---|
miR-29 family | Lung cancer and acute myeloid leukemia | DNMT3A DNMT3B | [85,86] |
AD | NAV3 | [84] | |
let-7 family | Lung cancer (Ras); Benign mesenchymal tumors and lung cancers (HMGA2); Burkitt lymphoma (Myc) | Ras HMGA2 Myc | [88,89,90,91] |
AD | APP | [87] | |
miR-106b family | Several cancers (p21/CDKN1A); breast cancer (BRMS1, RB) | p21/CDKN1A BRMS1 RB | [94,95] |
AD and PD | APP PTEN | [92,93] | |
miR-124a | Colon cancer | CDK6 RB | [99] |
PD | Unknown | [97,98] | |
miR-133b | Esophageal, lung and colon cancers | MCL1 BCL2L2 FSCN1 MET | [100,101,102,103] |
PD | PITX3 | [96] |
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Grasso, M.; Piscopo, P.; Confaloni, A.; Denti, M.A. Circulating miRNAs as Biomarkers for Neurodegenerative Disorders. Molecules 2014, 19, 6891-6910. https://doi.org/10.3390/molecules19056891
Grasso M, Piscopo P, Confaloni A, Denti MA. Circulating miRNAs as Biomarkers for Neurodegenerative Disorders. Molecules. 2014; 19(5):6891-6910. https://doi.org/10.3390/molecules19056891
Chicago/Turabian StyleGrasso, Margherita, Paola Piscopo, Annamaria Confaloni, and Michela A. Denti. 2014. "Circulating miRNAs as Biomarkers for Neurodegenerative Disorders" Molecules 19, no. 5: 6891-6910. https://doi.org/10.3390/molecules19056891