MiRNAs and neural stem cells: A team to treat parkinson disease?

RNA Biology

Volumn 9, Issue 6, 2012, Pages 720-730

  Palm, Thomas ^a   Bahnassawy, Lamia'a ^a   Schwamborn, Jens C ^a  

^a UNIVERSITY OF MÜNSTER   (Germany)

Author keywords

Differentiation; Micro RNA; Neural stem cells; Parkinson's disease; Regeneration

Indexed keywords

ALPHA SYNUCLEIN; BIOLOGICAL MARKER; LEUCINE RICH REPEAT KINASE 2; LEVODOPA; MICRORNA; MICRORNA 124; MICRORNA 132; MICRORNA 15B; MICRORNA 16; MICRORNA 221; MICRORNA 222; MICRORNA 9;

3' UNTRANSLATED REGION; BRAIN DEVELOPMENT; CELL DIFFERENTIATION; CELL FATE; CELL FUNCTION; CEREBELLUM; DIAGNOSTIC VALUE; DOPAMINERGIC NERVE CELL; EMBRYONIC STEM CELL; ENZYME PHOSPHORYLATION; FOREBRAIN; GENE INTERACTION; GENE MUTATION; HUMAN; INCIDENCE; LEWY BODY; NERVE DEGENERATION; NEURAL STEM CELL; NEUROBIOLOGY; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOPHYSIOLOGY; PLURIPOTENT STEM CELL; PROTEIN EXPRESSION; REVIEW; RNA ANALYSIS; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 84863436697     PISSN: 15476286     EISSN: 15558584     Source Type: Journal    
DOI: 10.4161/rna.19984     Document Type: Review

References (138)

1. Becher OJ, Holland EC. Evidence for and against regional differences in neural stem and progenitor cells of the CNS. Genes Dev 2010; 24:2233-8; PMID:20952533; http://dx.doi.org/10.1101/gad.1988010.
2. Saba R, Schratt GM. MicroRNAs in neuronal development, function and dysfunction. Brain Res 2010; 1338:3-13; PMID:20380818; http://dx.doi.org/10. 1016/j.brainres.2010.03.107.
3. Zhao C, Deng W, Gage FH. Mechanisms and functional 2012 implications of adult neurogenesis. Cell Landes 2008; 132:645-60; PMID:18295581; http://dx.doi.org/10.1016/j.cell.2008.01.033.
4. Berezikov E. Evolution of microRNA diversity and regulation in animals. Nat Rev Genet 2011; 12:846-60; PMID:22094948; http://dx.doi.org/10.1038/nrg3079.
5. Starega-Roslan J, Koscianska E, Kozlowski P, Krzyzosiak WJ. The role of the precursor structure in the biogenesis of microRNA. Cell Mol Life Sci 2011; 68:2859-71; PMID:21607569; http://dx.doi.org/10.1007/s00018-011-0726-2.
6. Okamura K, Hagen JW, Duan H, Tyler DM, Lai EC. The mirtron pathway generates microRNA-class regulatory RNAs in Drosophila. Cell 2007; 130:89-100; PMID:17599402; http://dx.doi.org/10.1016/j.cell.2007.06.028.
7. Ruby JG, Jan CH, Bartel DP. Intronic microRNA precursors that bypass Drosha processing. Nature 2007; 448:83-6; PMID:17589500; http://dx.doi.org/10. 1038/nature05983.
8. Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136:215-33; PMID:19167326; http://dx.doi.org/10.1016/j.cell.2009.01.002.
9. Peters L, Meister G. Argonaute proteins: mediators of RNA silencing. Mol Cell 2007; 26:611-23; PMID:17560368; http://dx.doi.org/10.1016/j.molcel.2007.05. 001.
10. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008; 9:102-14; PMID:18197166; http://dx.doi.org/10.1038/nrg2290.
11. Bak M, Silahtaroglu A, Møller M, Christensen M, Rath MF, Skryabin B, et al. MicroRNA expression in the adult mouse central nervous system. RNA 2008; 14:432-44; PMID:18230762; http://dx.doi.org/10.1261/rna.783108.
12. Olsen L, Klausen M, Helboe L, Nielsen FC, Werge T. MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats. PLoS One 2009; 4:7225; PMID:19806225; http://dx.doi.org/10.1371/journal.pone.0007225.
13. Natera-Naranjo O, Aschrafi A, Gioio AE, Kaplan BB. Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons. RNA 2010; 16:1516-29; PMID:20584895; http://dx.doi.org/10.1261/rna. 1833310.
14. Kye MJ, Liu T, Levy SF, Xu NL, Groves BB, Bonneau R, et al. Somatodendritic microRNAs identified by laser capture and multiplex RT-PCR. RNA 2007; 13:1224-34; PMID:17592044; http://dx.doi.org/10.1261/rna.480407.
15. Choi PS, Zakhary L, Choi WY, Caron S, Alvarez-Saavedra E, Miska EA, et al. Members of the miRNA-200 family regulate olfactory neurogenesis. Neuron 2008; 57:41-55; PMID:18184563; http://dx.doi.org/10.1016/j.neuron.2007.11.018.
16. Davis TH, Cuellar TL, Koch SM, Barker AJ, Harfe BD, McManus MT, et al. Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus. J Neurosci 2008; 28:4322-30; PMID:18434510; http://dx.doi.org/10.1523/JNEUROSCI.4815-07.2008.
17. De Pietri Tonelli D, Pulvers JN, Haffner C, Murchison EP, Hannon GJ, Huttner WB. miRNAs are essential for survival and differentiation of newborn neurons but not for expansion of neural progenitors during early neurogenesis in the mouse embryonic neocortex. Development 2008; 135:3911-21; PMID:18997113; http://dx.doi.org/10.1242/dev.025080.
18. Friedman LM, Dror AA, Mor E, Tenne T, Toren G, Satoh T, et al. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc Natl Acad Sci USA 2009; 106:7915-20; PMID:19416898; http://dx.doi.org/10.1073/pnas.0812446106.
19. Georgi SA, Reh TA. Dicer is required for the transition from early to late progenitor state in the developing mouse retina. J Neurosci 2010; 30:4048-61; PMID:20237275; http://dx.doi.org/10.1523/JNEUROSCI.4982-09.2010.
20. Zhao X, He X, Han X, Yu Y, Ye F, Chen Y, et al. MicroRNA-mediated control of oligodendrocyte differentiation. Neuron 2010; 65:612-26; PMID:20223198; http://dx.doi.org/10.1016/j.neuron.2010.02.018.
21. Huang T, Liu Y, Huang M, Zhao X, Cheng L. Wnt1-cre-mediated conditional loss of Dicer results in malformation of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation in mice. J Mol Cell Biol 2010; 2:152-63; PMID:20457670; http://dx.doi.org/10.1093/jmcb/mjq008.
22. Hébert SS, Papadopoulou AS, Smith P, Galas MC, Planel E, Silahtaroglu AN, et al. Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration. Hum Mol Genet 2010; 19:3959-69; PMID:20660113; http://dx.doi.org/10.1093/hmg/ddq311.
23. Kim J, Inoue K, Ishii J, Vanti WB, Voronov SV, Murchison E, et al. A MicroRNA feedback circuit in midbrain dopamine neurons. Science 2007; 317:1220-4; PMID:17761882; http://dx.doi.org/10.1126/science.1140481.
24. Gandhi PN, Chen SG, Wilson-Delfosse AL. Leucinerich repeat kinase 2 (LRRK2): a key player in the pathogenesis of Parkinson's disease. J Neurosci Res 2009; 87:1283-95; PMID:19025767; http://dx.doi.org/10.1002/jnr.21949.
25. de Rijk MC, Launer LJ, Berger K, Breteler MM, Dartigues JF, Baldereschi M, et al.; Neurologic Diseases in the Elderly Research Group. Prevalence of Parkinson's disease in Europe: A collaborative study of population-based cohorts. Neurology 2000; 54:21-3; PMID:10854357.
26. Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002; 14:223-36; PMID:11983801; http://dx.doi.org/10.1176/appi. neuropsych.14.2.223.
27. Abeliovich A, Flint Beal M. Parkinsonism genes: culprits and clues. J Neurochem 2006; 99:1062-72; PMID:16836655; http://dx.doi.org/10.1111/j.1471- 4159.2006.04102.x.
28. Jakes R, Spillantini MG, Goedert M. Identification of two distinct synucleins from human brain. FEBS Lett 1994; 345:27-32; PMID:8194594; http://dx.doi.org/10.1016/0014-5793(94)00395-5.
29. Mori F, Tanji K, Yoshimoto M, Takahashi H, Wakabayashi K. Demonstration of alpha-synuclein immunoreactivity in neuronal and glial cytoplasm in normal human brain tissue using proteinase K and formic acid pretreatment. Exp Neurol 2002; 176:98-104; PMID:12093086; http://dx.doi.org/10.1006/exnr.2002.7929.
30. Wislet-Gendebien S, Visanji NP, Whitehead SN, Marsilio D, Hou W, Figeys D, et al. Differential regulation of wild-type and mutant alpha-synuclein binding to synaptic membranes by cytosolic factors. BMC Neurosci 2008; 9:92; PMID:18808659; http://dx.doi.org/10.1186/1471-2202-9-92.
31. Sidhu A, Wersinger C, Moussa CE, Vernier P. The role of alpha-synuclein in both neuroprotection and neurodegeneration. Ann NY Acad Sci 2004; 1035:250-70; PMID:15681812; http://dx.doi.org/10.1196/annals.1332.016.
32. Wood-Kaczmar A, Gandhi S, Wood NW. Understanding the molecular causes of Parkinson's disease. Trends Mol Med 2006; 12:521-8; PMID:17027339; http://dx.doi.org/10.1016/j.molmed.2006.09.007.
33. Tan EK, Skipper LM. Pathogenic mutations in Parkinson disease. Hum Mutat 2007; 28:641-53; PMID:17385668; http://dx.doi.org/10.1002/humu.20507.
34. Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, et al. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000; 287:1265-9; PMID:10678833; http://dx.doi.org/10.1126/science.287.5456.1265.
35. Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Schindzielorz A, et al. Subcellular localization of wild-type and Parkinson's disease-associated mutant alpha-synuclein in human and transgenic mouse brain. J Neurosci 2000; 20:6365-73; PMID:10964942.
36. Saiki S, Sato S, Hattori N. Molecular pathogenesis of parkinson's disease: Update. J Neurol Neurosurg Psychiatry 2011; 83:430-6; PMID:22138181.
37. Giasson BI, Duda JE, Quinn SM, Zhang B, Trojanowski JQ, Lee VM. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 2002; 34:521-33; PMID:12062037; http://dx.doi.org/10.1016/S0896-6273(02)00682-7.
38. Giasson BI, Duda JE, Murray IV, Chen Q, Souza JM, Hurtig HI, et al. Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science 2000; 290:985-9; PMID:11062131; http://dx.doi.org/10.1126/science.290.5493.985.
39. Krüger R, Eberhardt O, Riess O, Schulz JB. Parkinson's disease: one biochemical pathway to fit all genes? Trends Mol Med 2002; 8:236-40; PMID:12067634; http://dx.doi.org/10.1016/S1471-4914(02)02333-X.
40. Junn E, Mouradian MM. Human alpha-synuclein overexpression increases intracellular reactive oxygen species levels and susceptibility to dopamine. Neurosci Lett 2002; 320:146-50; PMID:11852183; http://dx.doi.org/10.1016/S0304- 3940(02)00016-2.
41. Jiang H, Wu YC, Nakamura M, Liang Y, Tanaka Y, Holmes S, et al. Parkinson's disease genetic mutations increase cell susceptibility to stress: mutant alpha-synuclein enhances H2O2- and Sin-1-induced cell death. Neurobiol Aging 2007; 28:1709-17; PMID:16978743; http://dx.doi.org/10.1016/j. neurobiolaging.
42. Petrucelli L, O'Farrell C, Lockhart PJ, Baptista M, Kehoe K, Vink L, et al. Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons. Neuron 2002; 36:1007-19; PMID:12495618; http://dx.doi.org/10.1016/S0896-6273(02)01125- X.
43. Stefanis L, Larsen KE, Rideout HJ, Sulzer D, Greene LA. Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release and autophagic cell death. J Neurosci 2001; 21:9549-60; PMID:11739566.
44. Bennett MC, Bishop JF, Leng Y, Chock PB, Chase TN, Mouradian MM. Degradation of alpha-synuclein by proteasome. J Biol Chem 1999; 274:33855-8; PMID:10567343; http://dx.doi.org/10.1074/jbc.274.48.33855.
45. Webb JL, Ravikumar B, Atkins J, Skepper JN, Rubinsztein DC. Alpha-Synuclein is degraded by both autophagy and the proteasome. J Biol Chem 2003; 278:25009-13; PMID:12719433; http://dx.doi.org/10.1074/jbc.M300227200.
46. Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM. Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci USA 2009; 106:13052-7; PMID:19628698; http://dx.doi.org/10.1073/pnas.0906277106.
47. Wienholds E, Kloosterman WP, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E, et al. MicroRNA expression in zebrafish embryonic development. Science 2005; 309:310-1; PMID:15919954; http://dx.doi.org/10.1126/science. 1114519.
48. Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 2004; 5:13; PMID:15003116; http://dx.doi.org/10.1186/gb-2004-5-3- r13.
49. Doxakis E. Post-transcriptional regulation of alpha-synuclein expression by mir-7 and mir-153. J Biol Chem 2010; 285:12726-34; PMID:20106983; http://dx.doi.org/10.1074/jbc.M109.086827.
50. Ohmachi S, Watanabe Y, Mikami T, Kusu N, Ibi T, Akaike A, et al. FGF-20, a novel neurotrophic factor, preferentially expressed in the substantia nigra pars compacta of rat brain. Biochem Biophys Res Commun 2000; 277:355-60; PMID:11032730; http://dx.doi.org/10.1006/bbrc.2000.3675.
51. Ohmachi S, Mikami T, Konishi M, Miyake A, Itoh N. Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c. J Neurosci Res 2003; 72:436-43; PMID:12704805; http://dx.doi.org/10.1002/jnr.10592.
52. Rideout HJ, Dietrich P, Savalle M, Dauer WT, Stefanis L. Regulation of alpha-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons. J Neurochem 2003; 84:803-13; PMID:12562524; http://dx.doi.org/10.1046/j.1471-4159. 2003.01574.x.
53. Wang G, van der Walt JM, Mayhew G, Li YJ, Züchner S, Scott WK, et al. Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of alpha-synuclein. Am J Hum Genet 2008; 82:283-9; PMID:18252210; http://dx.doi.org/10.1016/j.ajhg.2007.09.021.
54. Jeffers M, Shimkets R, Prayaga S, Boldog F, Yang M, Burgess C, et al. Identification of a novel human fibroblast growth factor and characterization of its role in oncogenesis. Cancer Res 2001; 61:3131-8; PMID:11306498.
55. van der Walt JM, Noureddine MA, Kittappa R, Hauser MA, Scott WK, McKay R, et al. Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. Am J Hum Genet 2004; 74:1121-7; PMID:15122513; http://dx.doi.org/10.1086/421052.
56. Clarimon J, Xiromerisiou G, Eerola J, Gourbali V, Hellström O, Dardiotis E, et al. Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients. BMC Neurol 2005; 5:11; PMID:15967032; http://dx.doi.org/10.1186/1471-2377-5-11.
57. de Mena L, Cardo LF, Coto E, Miar A, Díaz M, Corao AI, et al. FGF20 rs12720208 SNP and microRNA-433 variation: no association with Parkinson's disease in Spanish patients. Neurosci Lett 2010; 479:22-5; PMID:20471450; http://dx.doi.org/10.1016/j.neulet.2010.05.019.
58. Galter D, Westerlund M, Carmine A, Lindqvist E, Sydow O, Olson L. LRRK2 expression linked to dopamine-innervated areas. Ann Neurol 2006; 59:714-9; PMID:16532471; http://dx.doi.org/10.1002/ana.20808.
59. Melrose H, Lincoln S, Tyndall G, Dickson D, Farrer M. Anatomical localization of leucine-rich repeat kinase 2 in mouse brain. Neuroscience 2006; 139:791-4; PMID:16504409; http://dx.doi.org/10.1016/j.neuroscience.2006.01.017.
60. Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci 2006; 29:286-93; PMID:16616379; http://dx.doi.org/10.1016/j.tins.2006.03.006.
61. Angeles DC, Gan BH, Onstead L, Zhao Y, Lim KL, Dachsel J, et al. Mutations in LRRK2 increase phosphorylation of peroxiredoxin 3 exacerbating oxidative stress-induced neuronal death. Hum Mutat 2011; 32:1390-7; PMID:21850687; http://dx.doi.org/10.1002/humu.21582.
62. Gehrke S, Imai Y, Sokol N, Lu B. Pathogenic LRRK2 negatively regulates microRNA-mediated translational repression. Nature 2010; 466:637-41; PMID:20671708; http://dx.doi.org/10.1038/nature09191.
63. Betschinger J, Mechtler K, Knoblich JA. Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 2006; 124:1241-53; PMID:16564014; http://dx.doi.org/10.1016/j.cell.2006.01. 038.
64. Schwamborn JC, Berezikov E, Knoblich JA. The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 2009; 136:913-25; PMID:19269368; http://dx.doi.org/10.1016/j.cell.2008.12.024.
65. Hillje AL, Worlitzer MM, Palm T, Schwamborn JC. Neural stem cells maintain their stemness through protein kinase Cζ-mediated inhibition of TRIM32. Stem Cells 2011; 29:1437-47; PMID:21732497.
66. Gillardon F, Mack M, Rist W, SchnackC, LenterM, HildebrandtT, et al. MicroRNA and proteome expression profiling in early-symptomatic α-synuclein (A30P)-transgenic mice. Proteomics Clin Appl 2008; 2:697-705; PMID:21136867; http://dx.doi.org/10.1002/prca.200780025.
67. Miñones-Moyano E, Porta S, Escaramís G, Rabionet R, Iraola S, Kagerbauer B, et al. MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet 2011; 20:3067-78; PMID:21558425; http://dx.doi.org/10. 1093/hmg/ddr210.
68. Santosh PS, Arora N, Sarma P, Pal-Bhadra M, Bhadra U. Interaction map and selection of microRNA targets in parkinson's disease-related genes. J Biomed Biotechnol 2009; 2009:363145.
69. Clarke DL, Johansson CB, Wilbertz J, Veress B, Nilsson E, Karlström H, et al. Generalized potential of adult neural stem cells. Science 2000; 288:1660-3; PMID:10834848; http://dx.doi.org/10.1126/science.288.5471.1660.
70. Zhang SC, Wernig M, Duncan ID, Brüstle O, Thomson JA. In vitro differentiation of transplantable neural precursors from human embryonic stem cells. Nat Biotechnol 2001; 19:1129-33; PMID:11731781; http://dx.doi.org/10. 1038/nbt1201-129.
71. Han SS, Williams LA, Eggan KC. Constructing and deconstructing stem cell models of neurological disease. Neuron 2011; 70:626-44; PMID:21609821; http://dx.doi.org/10.1016/j.neuron.2011.05.003.
72. Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, et al. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 2004; 101:18117-22; PMID:15608062; http://dx.doi.org/10.1073/pnas. 0408258102.
73. Ohira K. Injury-induced neurogenesis in the mammalian forebrain. Cell Mol Life Sci 2011; 68:1645-56; PMID:21042833; http://dx.doi.org/10.1007/s00018-010- 0552-y.
74. Doetsch F, García-Verdugo JM, Alvarez-Buylla A. Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA 1999; 96:11619-24; PMID:10500226; http://dx.doi.org/10.1073/pnas.96.20.11619.
75. Nakatomi H, Kuriu T, Okabe S, Yamamoto S, Hatano O, Kawahara N, et al. Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell 2002; 110:429-41; PMID:12202033; http://dx.doi.org/10.1016/S0092-8674(02)00862-0.
76. Lee SH, Lumelsky N, Studer L, Auerbach JM, McKay RD. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nat Biotechnol 2000; 18:675-9; PMID:10835609; http://dx.doi.org/10.1038/76536.
77. Kriks S, Shim JW, Piao J, Ganat YM, Wakeman DR, Xie Z, et al. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 2011; 480:547-51; PMID:22056989.
78. Jaeger I, Arber C, Risner-Janiczek JR, Kuechler J, Pritzsche D, Chen IC, et al. Temporally controlled modulation of FGF/ERK signaling directs midbrain dopaminergic neural progenitor fate in mouse and human pluripotent stem cells. Development 2011; 138:4363-74; PMID:21880784; http://dx.doi.org/10.1242/dev. 066746.
79. Chambers SM, Fasano CA, Papapetrou EP, Tomishima M, Sadelain M, Studer L. Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling. Nat Biotechnol 2009; 27:275-80; PMID:19252484; http://dx.doi.org/10.1038/nbt.1529.
80. Anokye-Danso F, Trivedi CM, Juhr D, Gupta M, Cui Z, Tian Y, et al. Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency. Cell Stem Cell 2011; 8:376-88; PMID:21474102; http://dx.doi.org/ 10.1016/j.stem.2011.03.001.
81. Miyoshi N, Ishii H, Nagano H, Haraguchi N, Dewi DL, Kano Y, et al. Reprogramming of mouse and human cells to pluripotency using mature microRNAs. Cell Stem Cell 2011; 8:633-8; PMID:21620789; http://dx.doi.org/10.1016/j.stem. 2011.05.001.
82. Kanellopoulou C, Muljo SA, Kung AL, Ganesan S, Drapkin R, Jenuwein T, et al. Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. Genes Dev 2005; 19:489-501; PMID:15713842; http://dx.doi.org/10.1101/gad.1248505.
83. Murchison EP, Partridge JF, Tam OH, Cheloufi S, Hannon GJ. Characterization of Dicer-deficient murine embryonic stem cells. Proc Natl Acad Sci USA 2005; 102:12135-40; PMID:16099834; http://dx.doi.org/10.1073/pnas. 0505479102.
84. Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet 2007; 39:380-5; PMID:17259983; http://dx.doi.org/10.1038/ng1969.
85. Bar M, Wyman SK, Fritz BR, Qi J, Garg KS, Parkin RK, et al. MicroRNA discovery and profiling in human embryonic stem cells by deep sequencing of small RNA libraries. Stem Cells 2008; 26:2496-505; PMID:18583537; http://dx.doi.org/10.1634/stemcells.2008-0356.
86. Morin RD, O'Connor MD, Griffith M, Kuchenbauer F, Delaney A, Prabhu AL, et al. Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. Genome Res 2008; 18:610-21; PMID:18285502; http://dx.doi.org/10.1101/gr.7179508.
87. Rosa A, Brivanlou AH. A regulatory circuitry comprised of miR-302 and the transcription factors OCT4 and NR2F2 regulates human embryonic stem cell differentiation. EMBO J 2011; 30:237-48; PMID:21151097; http://dx.doi.org/10. 1038/emboj.2010.319.
88. Liu DZ, Ander BP, Tian Y, Stamova B, Jickling GC, Davis RR, et al. Integrated analysis of mRNA and microRNA expression in mature neurons, neural progenitor cells and neuroblastoma cells. Gene 2012; 495:120-7; PMID:22244746; http://dx.doi.org/10.1016/j.gene.2011.12.041.
89. Kim HJ, Rosenfeld MG. Epigenetic control of stem cell fate to neurons and glia. Arch Pharm Res 2010; 33:1467-73; PMID:21052927; http://dx.doi.org/10. 1007/s12272-010-1001-z.
90. Lau P, Hudson LD. MicroRNAs in neural cell differentiation. Brain Res 2010; 1338:14-9; PMID:20382133; http://dx.doi.org/10.1016/j.brainres.2010.04. 002.
91. Leucht C, Stigloher C, Wizenmann A, Klafke R, Folchert A, Bally-Cuif L. MicroRNA-9 directs late organizer activity of the midbrain-hindbrain boundary. Nat Neurosci 2008; 11:641-8; PMID:18454145; http://dx.doi.org/10.1038/nn.2115.
92. Shibata M, Nakao H, Kiyonari H, Abe T, Aizawa S. MicroRNA-9 regulates neurogenesis in mouse telencephalon by targeting multiple transcription factors. J Neurosci 2011; 31:3407-22; PMID:21368052; http://dx.doi.org/10.1523/ JNEUROSCI.5085-10.2011.
93. Shibata M, Kurokawa D, Nakao H, Ohmura T, Aizawa S. MicroRNA-9 modulates Cajal-Retzius cell differentiation by suppressing Foxg1 expression in mouse medial pallium. J Neurosci 2008; 28:10415-21; PMID:18842901; http://dx.doi.org/10.1523/JNEUROSCI.3219-08.2008.
94. Krichevsky AM, Sonntag KC, Isacson O, Kosik KS. Specific microRNAs modulate embryonic stem cell-derived neurogenesis. Stem Cells 2006; 24:857-64; PMID:16357340; http://dx.doi.org/10.1634/stemcells.2005-0441.
95. Zhao C, Sun G, Li S, Shi Y. A feedback regulatory loop involving microRNA-9 and nuclear receptor TLX in neural stem cell fate determination. Nat Struct Mol Biol 2009; 16:365-71; PMID:19330006; http://dx.doi.org/10.1038/nsmb. 1576.
96. Lessard J, Wu JI, Ranish JA, Wan M, Winslow MM, Staahl BT, et al. An essential switch in subunit composition of a chromatin remodeling complex during neural development. Neuron 2007; 55:201-15; PMID:17640523; http://dx.doi.org/ 10.1016/j.neuron.2007.06.019.
97. Yoo AS, Sun AX, Li L, Shcheglovitov A, Portmann T, Li Y, et al. MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 2011; 476:228-31; PMID:21753754; http://dx.doi.org/10.1038/nature10323.
98. Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol 2002; 12:735-9; PMID:12007417; http://dx.doi.org/10.1016/S0960-9822(02)00809-6.
99. Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433:769-73; PMID:15685193; http://dx.doi.org/10.1038/ nature03315.
100. Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS. A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 2003; 9:1274-81; PMID:13130141; http://dx.doi.org/10.1261/rna.5980303.
101. Papagiannakopoulos T, Kosik KS. MicroRNA-124: micromanager of neurogenesis. Cell Stem Cell 2009; 4:375-6; PMID:19427286; http://dx.doi.org/10. 1016/j.stem.2009.04.007.
102. Cheng LC, Pastrana E, Tavazoie M, Doetsch F. miR-124 regulates adult neurogenesis in the subventricular zone stem cell niche. Nat Neurosci 2009; 12:399-408; PMID:19287386; http://dx.doi.org/10.1038/nn.2294.
103. Chen JS, Pedro MS, Zeller RW. miR-124 function during Ciona intestinalis neuronal development includes extensive interaction with the Notch signaling pathway. Development 2011; 138:4943-53; PMID:22028027; http://dx.doi.org/10. 1242/dev.068049.
104. Yu JY, Chung KH, Deo M, Thompson RC, Turner DL. MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation. Exp Cell Res 2008; 314:2618-33; PMID:18619591; http://dx.doi.org/10.1016/j.yexcr.2008.06.002.
105. Liu XS, Chopp M, Zhang RL, Tao T, Wang XL, Kassis H, et al. MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates proliferation of neural progenitor cells through Notch signaling pathway. PLoS One 2011; 6:23461; PMID:21887253; http://dx.doi.org/10.1371/journal.pone.0023461.
106. Hernández G, Vazquez-Pianzola P. Functional diversity of the eukaryotic translation initiation factors belonging to eIF4 families. Mech Dev 2005; 122:865-76; PMID:15922571; http://dx.doi.org/10.1016/j.mod.2005.04.002.
107. Strickland ER, Hook MA, Balaraman S, Huie JR, Grau JW, Miranda RC. MicroRNA dysregulation following spinal cord contusion: implications for neural plasticity and repair. Neuroscience 2011; 186:146-60; PMID:21513774; http://dx.doi.org/10.1016/j.neuroscience.2011.03.063.
108. Corsten MF, Miranda R, Kasmieh R, Krichevsky AM, Weissleder R, Shah K. MicroRNA-21 knockdown disrupts glioma growth in vivo and displays synergistic cytotoxicity with neural precursor cell delivered S-TRAIL in human gliomas. Cancer Res 2007; 67:8994-9000; PMID:17908999; http://dx.doi.org/10.1158/0008- 5472.CAN-07-1045.
109. Krichevsky AM, Gabriely G. miR-21: a small multifaceted RNA. J Cell Mol Med 2009; 13:39-53; PMID:19175699; http://dx.doi.org/10.1111/j.1582-4934.2008. 00556.x.
110. Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 2006; 29:77-103. (Pubitemid 44476840)
111. Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH. Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 2006; 29:77-103; PMID:16776580; http://dx.doi.org/10.1146/annurev.neuro.29.051605.112839.
112. Bruno IG, Karam R, Huang L, Bhardwaj A, Lou CH, Shum EY, et al. Identification of a microRNA that activates gene expression by repressing nonsense-mediated RNA decay. Mol Cell 2011; 42:500-10; PMID:21596314; http://dx.doi.org/10.1016/j.molcel.2011.04.018.
113. Smirnova L, Gräfe A, Seiler A, Schumacher S, NitschR, Wulczyn FG. Regulation of miRNA expression during neural cell specification. Eur J Neurosci 2005; 21:1469-77; PMID:15845075; http://dx.doi.org/10.1111/j.1460-9568.2005. 03978.x.
114. Bhuvanagiri M, Schlitter AM, Hentze MW, Kulozik AE. NMD: RNA biology meets human genetic medicine. Biochem J 2010; 430:365-77; PMID:20795950; http://dx.doi.org/10.1042/BJ20100699.
115. Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, et al. Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet 2007; 39:1127-33; PMID:17704778; http://dx.doi.org/10.1038/ng2100.
116. Addington AM, Gauthier J, Piton A, Hamdan FF, Raymond A, Gogtay N, et al. A novel frameshift mutation in UPF3B identified in brothers affected with childhood onset schizophrenia and autism spectrum disorders. Mol Psychiatry 2010; 16:238-9; PMID:20479756.
117. Laumonnier F, Shoubridge C, Antar C, Nguyen LS, Van Esch H, Kleefstra T, et al. Mutations of the UPF3B gene, which encodes a protein widely expressed in neurons, are associated with nonspecific mental retardation with or without autism. Mol Psychiatry 2010; 15:767-76; PMID:19238151; http://dx.doi.org/10. 1038/mp.2009.14.
118. Ambros V. A hierarchy of regulatory genes controls a larva-to-adult developmental switch in C. elegans. Cell 1989; 57:49-57; PMID:2702689; http://dx.doi.org/10.1016/0092-8674(89)90171-2.
119. Lee RC, FeinbaumRL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75:843-54; PMID:8252621; http://dx.doi.org/10.1016/0092-8674(93)90529-Y.
120. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 2000; 403:901-6; PMID:10706289; http://dx.doi.org/10.1038/35002607.
121. Abrahante JE, Daul AL, Li M, Volk ML, Tennessen JM, Miller EA, et al. The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell 2003; 4:625-37; PMID:12737799; http://dx.doi.org/10.1016/S1534-5807(03)00127-8.
122. Lin SY, Johnson SM, Abraham M, Vella MC, Pasquinelli A, Gamberi C, et al. The C. elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev Cell 2003; 4:639-50; PMID:12737800; http://dx.doi.org/10.1016/S1534-5807(03)00124-2.
123. Rybak A, Fuchs H, Smirnova L, Brandt C, Pohl EE, Nitsch R, et al. A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment. Nat Cell Biol 2008; 10:987-93; PMID:18604195; http://dx.doi.org/10.1038/ncb1759.
124. Zhao C, Sun G, Li S, Lang MF, Yang S, Li W, et al. MicroRNA let-7b regulates neural stem cell proliferation and differentiation by targeting nuclear receptor TLX signaling. Proc Natl Acad Sci USA 2010; 107:1876-81; PMID:20133835; http://dx.doi.org/10.1073/pnas.0908750107.
125. Laterza OF, Lim L, Garrett-Engele PW, Vlasakova K, Muniappa N, Tanaka WK, et al. Plasma MicroRNAs as sensitive and specific biomarkers of tissue injury. Clin Chem 2009; 55:1977-83; PMID:19745058; http://dx.doi.org/10.1373/clinchem. 2009.131797.
126. Weng H, Shen C, Hirokawa G, Ji X, Takahashi R, Shimada K, et al. Plasma miR-124 as a biomarker for cerebral infarction. Biomed Res 2011; 32:135-41; PMID:21551949; http://dx.doi.org/10.2220/biomedres.32.135.
127. Redell JB, Moore AN, Ward NH, 3rd, Hergenroeder GW, Dash PK. Human traumatic brain injury alters plasma microRNA levels. J Neurotrauma 2010; 27:2147-56; PMID:20883153; http://dx.doi.org/10.1089/neu.2010.1481.
128. Zeng L, Liu J, Wang Y, Wang L, Weng S, Tang Y, et al. MicroRNA-210 as a novel blood biomarker in acute cerebral ischemia [Elite Ed.]. Front Biosci (Elite Ed.) 2011; 3:1265-72; PMID:21622133.
129. Lai CY, Yu SL, Hsieh MH, Chen CH, Chen HY, Wen CC, et al. MicroRNA expression aberration as potential peripheral blood biomarkers for schizophrenia. PLoS One 2011; 6:21635; PMID:21738743; http://dx.doi.org/10.1371/ journal.pone.0021635.
130. Margis R, Margis R, Rieder CR. Identification of blood microRNAs associated to Parkinsonis disease. J Biotechnol 2011; 152:96-101; PMID:21295623; http://dx.doi.org/10.1016/j.jbiotec.2011.01.023.
131. Artner-Dworzak E, Lindner H, Puschendorf B. In vitro stability of human atrial natriuretic peptide (h-ANP). Clin Chim Acta 1991; 203:235-41; PMID:1723359; http://dx.doi.org/10.1016/0009-8981(91)90295-N.
132. Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9:654-9; PMID:17486113; http://dx.doi.org/10.1038/ncb1596.
133. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol 2011; 29:341-5; PMID:21423189; http://dx.doi.org/10.1038/nbt.1807.
134. Ebert MS, Neilson JR, Sharp PA. MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 2007; 4:721-6; PMID:17694064; http://dx.doi.org/10.1038/nmeth1079.
135. Krützfeldt J, Rajewsky N, Braich R, Rajeev KG, Tuschl T, Manoharan M, et al. Silencing of microRNAs in vivo with 'antagomirs'. Nature 2005; 438:685-9; PMID:16258535; http://dx.doi.org/10.1038/nature04303.
136. Jimenez-Mateos EM, Bray I, Sanz-Rodriguez A, Engel T, McKiernan RC, Mouri G, et al. miRNA Expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. Am J Pathol 2011; 179:2519-32; PMID:21945804; http://dx.doi.org/10.1016/j.ajpath.2011.07.036.
137. Elmén J, Lindow M, Schütz S, Lawrence M, Petri A, Obad S, et
138. Sun L, Zhang D, Liu F, Xiang X, Ling G, Xiao L, et al. Low-dose paclitaxel ameliorates fibrosis in the remnant kidney model by downregulating miR-192. J Pathol 2011; 225:364-77; PMID:21984124; http://dx.doi.org/10.1002/ path.2961.