MicroRNA-Directed Neuronal Reprogramming as a Therapeutic Strategy for Neurological Diseases
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The loss of neurons due to injury and disease results in a wide spectrum of highly disabling neurological and neurodegenerative conditions, given the apparent limited capacity of endogenous repair of the adult central nervous system (CNS). Therefore, it is important to develop technologies that can promote de novo neural stem cell and neuron generation. Current insights in CNS development and cellular reprogramming have provided the knowledge to finely modulate lineage-restricted transcription factors and microRNAs (miRNA) to elicit correct neurogenesis. Here, we discuss the current knowledge on the direct reprogramming of somatic non-neuronal cells into neural stem cells or subtype specific neurons in vitro and in vivo focusing on miRNA driven reprogramming. miRNA can allow rapid and efficient direct phenotype conversion by modulating gene networks active during development, which promote global shifts in the epigenetic landscape pivoting cell fate decisions. Furthermore, we critically present state-of-the-art and recent advances on miRNA therapeutics that can be applied to the diseased CNS. Together, the advances in our understanding of miRNA role in CNS development and disease, recent progress in miRNA-based therapeutic strategies, and innovative drug delivery methods create novel perspectives for meaningful therapies for neurodegenerative disorders.
KeywordsNeuronal repair Therapeutics microRNA Reprogramming Neural stem cells Neurons
The authors wish to thank the Associazione Centro Dino Ferrari for their support.
IF and SC conceived the idea, revised all the literature, and contributed to all parts. All authors read and approved the final manuscript.
Compliance with Ethical Standards
Conflict of Interests
The authors declare that they have no conflict of interest.
AriSLA provided financial support to SC through a research grant (AriSLAsmallRNALS). AriSLA had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript: and in the decision to publish the results.
- 1.Dametti S, Faravelli I, Ruggieri M et al (2015) Experimental advances towards neural regeneration from induced stem cells to direct in vivo reprogramming. Mol Neurobiol. doi: 10.1007/s12035-015-9181-7
- 22.Yang H, Zhang L, An J et al (2016) MicroRNA-mediated reprogramming of somatic cells into neural stem cells or neurons. Mol Neurobiol. doi: 10.1007/s12035-016-0115-9
- 40.Gu X, Fu C, Lin L et al (2017) miR-124 and miR-9 mediated downregulation of HDAC5 promotes neurite development through activating MEF2C-GPM6A pathway. J Cell Physiol. doi: 10.1002/jcp.25927
- 61.Zhou X, Yang P-C (2012) MicroRNA: a small molecule with a big biological impact. MicroRNA Shariqah United Arab Emir 1:1Google Scholar