Macro Roles for MicroRNAs in the Life and Death of Neurons by Kenneth S. Kosik, Thales Papagiannakopoulos (auth.), Bart De

By Kenneth S. Kosik, Thales Papagiannakopoulos (auth.), Bart De Strooper, Yves Christen (eds.)

The discovery of microRNAs has printed an unforeseen and incredible extra point of excellent tuning of the genome and the way genes are used repeatedly in numerous mixtures to generate the complexity that underlies for example the mind. because the preliminary stories played in C.elegans, we've long gone a much solution to start to know the way microRNA pathways may have an impression on well-being and sickness in human. even if microRNAs are abundantly expressed within the mind, fairly little is understood in regards to the a number of services of those RNA molecules within the frightened procedure. however, we all know already that microRNA pathways play significant roles within the proliferation, differentiation, functionality and upkeep of neuronal cells. a number of exciting reports have associated microRNAs as significant regulators of the neuronal phenotype, and feature implicated particular microRNAs within the legislation of synapse formation and plasticity. disorder of microRNA pathways can be slowly rising as a possible vital contributor to the pathogenesis of significant neurodegenerative issues corresponding to Alzheimer’s sickness and Parkinson’s disorder. those novel insights seem to be specific promising for the knowledge of the very common and badly understood sporadic sorts of those illnesses in comparison to the genetic types. therefore, the higher realizing of the consequences of this novel box of molecular biology is essential for the huge sector of neurosciences, from the basic features to the health center, and from novel diagnostic to possibly healing purposes for serious neurological and perhaps psychiatric illnesses.

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Extra info for Macro Roles for MicroRNAs in the Life and Death of Neurons

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MTOR signaling) triggers post-translational modification(s) of key components of the miR-134-associated silencing complex (miRISC). This hypothesis is supported by the recent observations of Ago2 phosphorylation by MAPK, calpain-mediated Dicer cleavage and memory-induced degradation of the RISC helicase Armitage (Lugli et al. 2005; Ashraf et al. 2006; Zeng et al. 2008). In addition to these core components of RISC, sequence-specific RNA-binding proteins associated with the Limk1 30 UTR could modulate miR-134 activity.

To further complicate matters, mature miR-138 is derived from two individual genomic loci, and thus the relative contribution of the different pri-miR-138 transcripts to the generation of mature miR-138 in neurons under basal and activity conditions will need to be determined. In conclusion, additional experiments are required to explore the relevance of activity-dependent miR-138 expression for the dynamic remodeling of dendritic spines. 2 Activity-dependent regulation of miRNA-associated complexes Our findings that BDNF was able to release miR134 inhibition of Limk1 mRNA translation provided one of the first examples that the activity of mature miRNAs can be regulated by extrinsic stimuli (Fig.

Edu B. de Strooper and Y. 1007/978-3-642-04298-0_4, # Springer-Verlag Berlin Heidelberg 2010 27 28 A. Abeliovich in vivo (Kosik and Krichevsky 2005; Krichevsky et al. 2003) or in the context of embryonic stem (ES) cell cultures (Krichevsky et al. 2006). More recently, a mammalian miRNA was identified that regulates neurite morphology in embryonic hippocampal neuron cultures (Schratt et al. 2006). Embryonic and neuronal stem cells are capable of differentiating to the mDN phenotype in vitro and thus offer a potentially simplified model system for the analysis of mDN maturation relative to the intact mammalian CNS.

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