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MicroRNAs and Regeneration in Animal Models of CNS Disorders

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Abstract

microRNAs (miRNAs) are recently identified small RNA molecules that regulate gene expression and significantly influence the essential cellular processes associated with CNS repair after trauma and neuropathological conditions including stroke and neurodegenerative disorders. A number of specific miRNAs are implicated in regulating the development and propagation of CNS injury, as well as its subsequent regeneration. The review focuses on the functions of the miRNAs and their role in brain recovery following CNS damage. The article introduces a brief description of miRNA biogenesis and mechanisms of miRNA-induced gene suppression, followed by an overview of miRNAs involved in the processes associated with CNS repair, including neuroprotection, neuronal plasticity and axonal regeneration, vascular reorganization, neuroinflammation, and endogenous stem cell activation. Specific emphasis is placed on the role of multifunctional miRNA miR-155, as it appears to be involved in multiple neurorestorative processes during different CNS pathologies. In association with our own studies on miR-155, I introduce a new and unexplored approach to cerebral regeneration: regulation of brain tissue repair through a direct modulation of specific miRNA activity. The review concludes with discussion on the challenges and the future potential of miRNA-based therapeutic approaches to CNS repair.

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Abbreviations

NogoA:

Neurite outgrowth inhibitor

TGF-β:

Transforming growth factor beta

VEGF:

Vascular endothelial growth factor

VE:

Cadherin-vascular endothelial cadherin

TBI:

Traumatic brain injury

Rheb:

Ras homolog enriched in brain

mTOR:

Mammalian target of rapamycin

Rictor:

Rapamycin-insensitive companion of mammalian target of rapamycin

C/EBP-β:

CCAAT/enhancer-binding protein beta

BMP:

Bone morphogenetic protein

NO:

Nitric oxide

JAK:

Janus kinase

STAT:

Signal transducers and activators of transcription

SOCS:

Suppressor of cytokine signaling

SHIP:

Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase

LPS:

Lipopolysaccharide

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This work was supported by the National Institute of Neurological Disorders and Stroke-NIH R01NS082225 Grant.

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  1. Department of Neurosurgery, University of New Mexico Health Sciences Center, 1101 Yale Blvd, Albuquerque, NM, 87106-3834, USA

    Tamara Roitbak

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Roitbak, T. MicroRNAs and Regeneration in Animal Models of CNS Disorders. Neurochem Res 45, 188–203 (2020). https://doi.org/10.1007/s11064-019-02777-6

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