Immune cell influences on neuronal viability and repair

Principal Investigator: Dr. Alyson Fournier

Affiliation: Montreal Neurological Institute

Term: April 1, 2016 – March 31, 2019

Funding: $370,512

Keywords: neurodegeneration, miRNA, neuroprotection, EAE, progressive MS

Summary:

  • microRNAs are molecules which have been implicated in regulating neurons in response to inflammatory stimuli. They have the ability to silence the expression of many genes at once.
  • Whether microRNAs can silence many genes that prevent nerve cell repair simultaneously is unknown.
  • The research team will:
    • Identify miRNAs that are regulated in response to MS-related stimuli and that may affect the degeneration, viability and regenerative potential of injured brain cells.

Project Description:

One characteristic of MS is damage to nerve cells, which disrupts communication within the central nervous system and the body and the failure of nerve cells to repair themselves. All this results in sustained disability.Additionally, the environment in the MS brain is not permissive for nerve cell repair. The aim of Dr. Alyson Fournier’s work is to better understand the signals that limit repair and to use this information to develop molecular therapeutics to promote nerve cell repair. To do so, the team is looking at microRNAs which are small molecules found in plants, and animals that silence broad programs of gene expression. Targeting of microRNAs would thus affect the expression of many genes that are important for nerve cell repair simultaneously. In the past couple of years, the research team has identified small molecules that target a particular family of proteins called, 14-3-3, to promote repair of damaged axons in a model of nerve injury. These small molecules represent excellent candidates for mediating neuronal repair in the context of neuroinflammation. In the next year, the team will be manipulating the expression and activity of miRNAs and 14-3-3s in pre-clinical models of central nervous system inflammation to assess their ability to promote neuronal protection and repair.

Potential Impact: The use of molecular therapeutics to promote nerve cell protection and repair in combination with current therapies targeting immune dysfunction will lead to improved outcomes for MS patients.

Project Status: In Progress

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