MicroRNAs in neurodegeneration

Temasek Life Sciences Laboratory, 1 Research Link, Singapore 117604, Singapore.
Current Opinion in Neurobiology (Impact Factor: 6.63). 09/2008; 18(3):292-6. DOI: 10.1016/j.conb.2008.07.001
Source: PubMed

ABSTRACT microRNAs (miRNAs) act as post-transcriptional regulators of gene expression in diverse cellular and developmental processes. Many miRNAs are expressed specifically in the central nervous system, where they have roles in differentiation, neuronal survival, and potentially also in plasticity and learning. The absence of miRNAs in a variety of specific postmitotic neurons can lead to progressive loss of these neurons and behavioral defects reminiscent of the phenotypes seen in the pathologies of neurodegenerative diseases. Here, we review recent studies which provide a link between miRNA function and neurodegeneration. We also discuss evidence which might suggest involvement of miRNAs in the emergence or progression of neurodegenerative diseases.

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    • "In terms of neurodegeneration, many studies have directly addressed the role of miRNAs in the development and regulation of the nervous system (reviewed in Schaefer et al., 2007; Bushati and Cohen, 2008; Barbato et al., 2009; Hebert and De Strooper, 2009; Martino et al., 2009; Roshan et al., 2009; Weinberg and Wood, 2009; Lau and de Strooper 2010). It has also been reported that the dysfunction of brain-enriched miRNAs specifically targeting and regulating the expression of disease-associated genes may lead to neurodegeneration and that disease-linked proteins may regulate the miRNA machinery (Savas et al., 2008; Gehrke et al., 2010; Esteller, 2011). "
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    ABSTRACT: Trinucleotide repeat expansion disorders (TREDs) constitute a group of dominantly inherited neurological diseases that are incurable and ultimately fatal. The underlying cause of TREDs is an expansion of trinucleotide repeats that may occur in the coding and non-coding regions of human genes. MicroRNAs (miRNAs) have emerged as potent regulators of gene expression at the posttranscriptional level. They are involved in a variety of physiological and pathological processes in humans, and the alteration of miRNA expression is considered to be a hallmark of many diseases, including TREDs. This review summarizes the current knowledge regarding the involvement of miRNAs in the pathogenesis of TREDs and the experimentally proven associations between specific miRNAs and particular disorders that have been reported to date.
    Applied RNAi: From Fundamental Research to Therapeutic Applications, Edited by Patrick Arbuthnot, Marc S. Weinberg, 06/2014: chapter 12: pages 227–246; Caister Academic Press., ISBN: 978-1-908230-43-0 / Ebook 978-1-908230-67-6
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    • "Conditional knockout of the miRNA biosynthetic enzyme Dicer in the developing mouse brain has demonstrated that miRNAs have a critical role in neuronal survival in various brain regions [22], [23], [24], [25], including the hippocampus [26], [27], [28], [29]. Likewise, disruption of Dicer at later time points suggests that alterations in miRNA expression are associated with the degeneration of mature neurons in mice [30], [31]. Others have shown that miRNAs can play fundamentally important roles in more specific neurobiological processes such as proliferation, differentiation, neurite growth and apoptosis [8], [32], [33], [34]. "
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    ABSTRACT: MicroRNAs (miRNAs) are evolutionarily conserved non-coding RNAs of ∼22 nucleotides that regulate gene expression at the level of translation and play vital roles in hippocampal neuron development, function and plasticity. Here, we performed a systematic and in-depth analysis of miRNA expression profiles in cultured hippocampal neurons during development and after induction of neuronal activity. MiRNA profiling of primary hippocampal cultures was carried out using locked nucleic-acid-based miRNA arrays. The expression of 264 different miRNAs was tested in young neurons, at various developmental stages (stage 2-4) and in mature fully differentiated neurons (stage 5) following the induction of neuronal activity using chemical stimulation protocols. We identified 210 miRNAs in mature hippocampal neurons; the expression of most neuronal miRNAs is low at early stages of development and steadily increases during neuronal differentiation. We found a specific subset of 14 miRNAs with reduced expression at stage 3 and showed that sustained expression of these miRNAs stimulates axonal outgrowth. Expression profiling following induction of neuronal activity demonstrates that 51 miRNAs, including miR-134, miR-146, miR-181, miR-185, miR-191 and miR-200a show altered patterns of expression after NMDA receptor-dependent plasticity, and 31 miRNAs, including miR-107, miR-134, miR-470 and miR-546 were upregulated by homeostatic plasticity protocols. Our results indicate that specific miRNA expression profiles correlate with changes in neuronal development and neuronal activity. Identification and characterization of miRNA targets may further elucidate translational control mechanisms involved in hippocampal development, differentiation and activity-depended processes.
    PLoS ONE 10/2013; 8(10):e74907. DOI:10.1371/journal.pone.0074907 · 3.23 Impact Factor
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    • "MicroRNAs, often propounded as being “micro in size, macro in function” [16], have been found to be implicated in various vital processes. The wide range of processes, which are reported to be regulated by miRNAs, are cell differentiation, development, stress resistance [17], and several processes in neurodegenerative disorders [18–20]. Growing evidence about the role of microRNAs in neurodegenerative disorders has incited innumerable studies across the globe. "
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    ABSTRACT: Amyotrophic Lateral Sclerosis (ALS) is a rare neurological disease affecting mainly motor neurons and often leads to paralysis and death in extreme cases. For exploring the role of microRNAs in genes regulation in ALS disease, miRanda was employed for prediction of target sites of miRNAs expressed in various parts of brain and CNS on 35 genes associated with ALS. Similar search was conducted using TargetScan and PicTar for prediction of target sites in 3' UTR only. 1456 target sites were predicted using miRanda and more target sites were found in 5' UTR and CDS region as compared to 3' UTR. 11 target sites were predicted to be common by all the algorithms and, thus, these represent the most significant sites. Target site hotspots were identified and were recognized as hotspots for multiple miRNAs action, thus, acting as favoured sites of action for the repression of gene expression. The complex interplay of genes and miRNAs brought about by multiplicity and cooperativity was explored. This investigation will aid in elucidating the mechanism of action of miRNAs for the considered genes. The intrinsic network of miRNAs expressed in nervous system and genes associated with ALS may provide rapid and effective outcome for therapeutic applications and diagnosis.
    International Journal of Plant Genomics 07/2013; 2013:383024. DOI:10.1155/2013/383024
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