MicroRNAs and neurodegeneration: Role and impact

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Trends in cell biology (Impact Factor: 12.01). 09/2012; 23(1). DOI: 10.1016/j.tcb.2012.08.013
Source: PubMed


Neurodegenerative diseases are typically late-onset, progressive disorders that affect neural function and integrity. Although most attention has been focused on the genetic underpinnings of familial disease, mechanisms are likely to be shared with more predominant sporadic forms, which can be influenced by age, environment, and genetic inputs. Previous work has largely addressed the roles of select protein-coding genes; however, disease pathogenesis is complicated and can be modulated through not just protein-coding genes, but also regulatory mechanisms mediated by the exploding world of small non-coding RNAs. Here, we focus on emerging roles of miRNAs in age-associated events impacting long-term brain integrity and neurodegenerative disease.

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    • "MicroRNAs may modulate diverse aspects of neurodegeneration by acting as molecular 'on–off' switches. In particular, microRNAs involved with focal adhesion (miR-20a), regulation of MAPK signaling (miR- 181b, -21, -29b) and neurogenesis (miR-133, -103, -107, -124) have been shown to be dysregulated at the onset of neurodegeneration (Babar et al., 2008; Hebert et al., 2009; Marsit et al., 2006; Masashi and Bonini, 2013). It is possible that selected microRNAs may be acting to repress pro-neurodegeneration genes and microRNAs may have integral neuronal roles to play in torpor. "
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    ABSTRACT: Recent research has highlighted roles for non-coding RNA i7n the regulation of stress tolerance in bats. In this study, we propose that microRNA could also play an important role in neuronal maintenance during hibernation. To explore this possibility, RT-PCR was employed to investigate the expression of eleven microRNAs from the brain tissue of euthermic control and torpid bats. Results show that eight microRNAs (miR-21, -29b, -103, -107, -124a, -132, -183 and -501) increased (1.2–1.9 fold) in torpid bats, while the protein expression of Dicer, a microRNA processing enzyme, did not significantly change during torpor. Bioinformatic analysis of the differentially expressed microRNA suggests that these microRNAs are mainly involved in two processes: (1) focal adhesion and (2) axon guidance. To determine the extent of microRNA sequence conservation in the bat, we successfully identified bat microRNA from sequence alignments against known mouse (Mus musculus) microRNA. We successfully identified 206 conserved pre-microRNA sequences, leading to the identification of 344 conserved mature microRNA sequences. Sequence homology of the identified sequences was found to be 94.76 ± 3.95% and 98.87 ± 2.24% for both pre- and mature microRNAs, respectively. Results suggest that brain function related to the differentiation of neurons and adaptive neuroprotection may be under microRNA control during bat hibernation.
    Gene 07/2014; 544(1):67–74. DOI:10.1016/j.gene.2014.04.048 · 2.14 Impact Factor
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    • "MiRNAs play a crucial role in epigenetic gene regulation and have been linked to development and differentiation, cell growth and cell death [2-5]. They are misregulated in several disorders, including neurodegenerative diseases, cardio-vascular diseases and cancer [2-5]. MiRNAs are small, non-coding single stranded RNAs, 21-25 nucleotides in length that are generated from a primary miRNA transcript (pri-miRNA). "
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    ABSTRACT: MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally silence target mRNAs. Dysregulation of miRNAs is a frequent event in several diseases, including cancer. One miRNA that has gained special interest in the field of cancer research is miRNA-125b (miR-125b). MiR-125b is a ubiquitously expressed miRNA that is aberrantly expressed in a great variety of tumors. In some tumor types, e.g. colon cancer and hematopoietic tumors, miR-125b is upregulated and displays oncogenic potential, as it induces cell growth and proliferation, while blocking the apoptotic machinery. In contrast, in other tumor entities, e.g. mammary tumors and hepatocellular carcinoma, miR-125b is heavily downregulated. This downregulation is accompanied by de-repression of cellular proliferation and anti-apoptotic programs, contributing to malignant transformation. The reasons for these opposing roles are poorly understood. We summarize the current knowledge of miR-125b and its relevant targets in different tumor types and offer several hypotheses for the opposing roles of miR-125b: miR-125b targets multiple mRNAs, which have diverse functions in individual tissues. These target mRNAs are tissue and tumor specifically expressed, suggesting that misregulation by miR-125b depends on the levels of target gene expression. Moreover, we provide several examples that miR-125b upregulation dictates oncogenic characteristics, while downregulation of miR-125b corresponds to the loss of tumor suppressive functions. Thus, in different tumor entities increased or decreased miR-125b expression may contribute to carcinogenesis.
    Cell Communication and Signaling 04/2014; 12(1):30. DOI:10.1186/1478-811X-12-30 · 3.38 Impact Factor
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    • "Since alterations in miRNAs expression levels were found in numerous neurodegenerative diseases (Abe and Bonini, 2013; Junn and Mouradian, 2012), miRNAs are emerging as key players in the process of neurodegeneration, and as potential targets for therapeutic intervention. "
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    ABSTRACT: Molecular genetics insight into the pathogenesis of several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, encourage direct interference with the activity of neurotoxic genes or the molecular activation of neuroprotective pathways. Oligonucleotide-based therapies are recently emerging as an efficient strategy for drug development and these can be employed as new treatments of neurodegenerative states. Here we review advances in this field in recent years which suggest an encouraging assessment that oligonucleotide technologies for targeting of RNAs will enable the development of new therapies and will contribute to preservation of brain integrity.
    Brain research 04/2014; 1584. DOI:10.1016/j.brainres.2014.04.005 · 2.84 Impact Factor
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