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The role of small RNAs in remyelination

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The regulation of neurodegeneration

Delineation of the molecular mechanisms implicated in the process of myelination could help design novel targeted therapies for neurodegenerative disorders.

Health

Many diseases of the central nervous system, such as multiple sclerosis (MS), are associated with a loss of the insulating myelin sheath around neuronal axons. This demyelination impairs transmission of nerve impulses and thus the body cannot properly communicate signals. At the initial stages of MS, an attempt to remyelinate axons is observed but this process fails, and axons ultimately become damaged. In an experimental setting, the process of remyelination is linked with activation and differentiation of oligodendrocyte precursors (OPCs). During OPC differentiation certain genes are switched on through the concerted action of transcriptional activators, repressors and miRNAs. The EU-funded project 'The role of small RNAs in remyelination' (SRNAS REMYELINATION) concentrated on the regulatory role of miRNA and other epigenetic regulators in neurodegeneration and neuroprotection. In this context, scientists used transgenic animals with a deletion in Dicer or Pasha, key molecules responsible for the maturation of small RNAs (sRNAs). It is possible to induce and carefully control the demyelination process in these animals by injecting the substance lysolecithin. Following experimentally induced demyelination, researchers observed that the protein Pasha, which is required for correct miRNA processing, was instrumental in maintaining a functional neuronal network. Mice lacking the Pasha-encoding gene DGCR8 induced a Parkinsonism-like neuropathology associated with abnormal myelin deposits and axonal degeneration in the white matter of the spinal cord. These findings prompted scientists to steer their work towards the identification of the miRNA molecules responsible for this phenotype. Coupled with investigation of the affected signalling pathways, the SRNAS REMYELINATION study aims to provide important insight into demyelination and identify neuroprotective molecules.

Keywords

Neurodegeneration, myelination, central nervous system, myelin sheath, neuronal axons, remyelination, small RNAs, SRNAS, miRNA, neuroprotection, Dicer, Pasha, axonal degeneration, signalling pathways

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