miRNA
Jump to:
Introduction
Research Reviews
Additional Supporting Publications
Neurodegenerative disease is the result of deterioration of neurons, ultimately leading to disabilities and the possibility of death. There are dozens of identified neurodegenerative diseases, and research suggests that gene defects play a major role in disease pathogenesis. Genetic studies, to date, have provided valuable clues into the etiology and pathogenesis of many neurodegenerative diseases from a molecular perspective, but there is significant work to be done before a full picture can be obtained. Due to the lack of comprehensive information on these diseases, cases thought to be unique and unrelated to family inheritance, might eventually prove to originate from specific genetic mutations or genetic risk factors. Further, the possibility exists that there may be only a few common genetic and mechanistic factors contributing to neuronal cell death. Future studies examining the genetic basis of neurodegeneration will truly be the key to gleaning information for the design and development of early prediction, prevention, and treatment options for addressing these diseases.* The study of miRNA is a novel approach to understanding neurodegenerative disease and recent studies have hinted at miRNA-linked modulation of long term neuron integrity in response to toxic human disease proteins associated with neurodegenerative diseases. Traditionally, miRNA expression has been tested using low-throughput techniques such as Northern-blot analysis and real-time PCR, but new developments in microarray technology now enable global profiling of all miRNA genes and their precursors in any sample type.
* For an excellent review of the genetic epidemiology of neurodegenerative disease, review Bertram L, Tanzi RE. J Clin Invest. 2005 Jun;115(6):1449-57.
In a review by Julide Bilen and colleagues at the University of Pennsylvania (2006), the role of microRNA pathways and their role in the modulation of degeneration induced by pathogenic human diseases, is thoroughly discussed. The group presents results from their recent work involving the isolation of the miRNA bantam (ban) in a genetic screen for modulators of pathogenicity of a human neurodegenerative disease model in Drosophila. Their studies demonstrated that upregulation of ban mitigated degeneration induced by the pathogenic polyglutamine (polyQ) protein Ataxin 3, which was mutated in the human polyglutamine disease spinocerebellar ataxia type 3 (SCA3). To address the broader role for miRNAs in neuroprotection, the group also showed that loss of all miRNAs, by dicer mutation, dramatically enhances pathogenic polyQ protein toxicity in flies and in human HeLa cells. These studies suggest that miRNAs may be important for neuronal survival in the context of human neurodegenerative disease, providing the foundation for identifying the miRNAs involved in neurodegenerative disease, and the biological pathways affected.
Title: A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins.
Authors: Bilen J, Liu N, Bonini NM
Journal: Cell Cycle, Vol 5, Issue 24: 2835-8
More
Dostie and researchers (2003) reported on the characterization of miRNAs associated with miRNPs (microribonucleoproteins) isolated from neuronal cells. Deletion or loss-of-function mutations in Survival of Motor Neuron (SMN) proteins cause spinal muscular atrophy (SMA), a common genetic disease characterized by progressive degeneration of motor neurons. Gemin3 and Gemin4 are shared components of the SMN and miRNP complexes, deletion or loss-of-function mutations of SMN in SMA may also affect the activity of miRNPs due to possible redistribution or changes in the levels of Gemin3 and Gemin4. Thus, it is possible that specific or general changes in the activity of the miRNPs play a role in the development of SMA. In this study, the researchers used RNA immunoprecipitation, 3'-end labeling, and miRNA cloning to identify 53 novel miRNAs from mouse and human neuronal cell lines, several of which were phylogenetically conserved in divergent organisms. Several miRNAs were found to constitute distinct subfamilies comprising multiple copies on different chromosomes, suggesting that these miRNAs play an important role in the regulation of gene expression.
Title: Numerous microRNPs in neuronal cells containing novel microRNAs.
Authors: Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G
Journal: RNA, Vol 9, Issue 2: 180-6
More
Rodriguez-Lebron and Paulson (2006) review allele-specific RNA interference for neurological disease, discussing suppression of toxic gene expression through RNAi for the treatment of human disease and the characterization of neurological disorders. The researchers review strategies used to achieve allele-specific silencing in light of recent developments in the field of RNAi biology. In particular, new insights into siRNA and miRNA processing are discussed as a means to improve efficiency and specificity of RNAi therapy. In addition, the team discusses steps that can be taken to maximize the therapeutic benefits of this powerful technology. The research described in this review indicates that future work should include the development and testing of reagents that mirror features of endogenously expressed miRNAs in order to effectively develop optimal therapies for neurological disease.
Title: Allele-specific RNA interference for neurological disease.
Authors: Rodriguez-Lebron E, Paulson HL
Journal: Gene Ther, Vol 13, Issue 6: 576-81
More
Title: MicroRNA pathways modulate polyglutamine-induced neurodegeneration.
Authors: Bilen J, Liu N, Burnett BG, Pittman RN, Bonini NM
Journal: Mol Cell, Vol 24, Issue 1: 157-63
More
Title: The neuronal microRNA system.
Authors: Kosik KS
Journal: Nat Rev Neurosci, Vol 7, Issue 12: 911-20
More
Title: The Hippo pathway regulates the bantam microRNA to control cell proliferation and apoptosis in Drosophila.
Authors: Thompson BJ, Cohen SM
Journal: Cell, Vol 126, Issue 4: 767-74
More
Title: MicroRNA: microRNAs reach out into dendrites.
Authors: Tai HC, Schuman EM
Journal: Curr Biol, Vol 16, Issue 4: R121-3
More
To search the full database of miRNA papers, click here.