Characterizing the neuroprotective roles of bHLH proteins Npas4 and ARNT2 in inflammatory neurodegeneration related to multiple sclerosis

Principal Investigator: Dr. Jacqueline Quandt

Affiliation: University of British Columbia

Year awarded: 2018-2019

Amount Awarded: $346,400

Keywords: Axonal Damage, Neurodegeneration, Npas4, ARNT2


  • In multiple sclerosis (MS), damage to nerve fibers and death of neurons occurs in the brain and spinal cord.
  • The molecules regulating this destruction in MS are unknown.
  • The research team will:
    • Evaluate how two molecules, previously identified to play a role in damage to nerve fibers and death of neurons, influence disease course in animal models of MS.
    • Determine if increasing or reducing the function of the two molecules could identify additional mediators that regulate these processes in MS.

Project Description:

Damage to nerve fibers along with degeneration and death of neurons (neurodegeneration) are associated with chronic disability in MS. Dr. Jacqueline Quandt and her research team aim to characterize the role of neuronal PAS4 (Npas4) and aryl hydrocarbon receptor nuclear translocator (ARNT2), two molecules with an established role in damage of nerve fibers and neurodegeneration. These molecules have neuroprotective properties, the potential to influence the earliest steps of neurodegeneration at disease onset, as well as the potential to contribute to recovery while limiting progression in MS. From a previous grant, also supported by the MS Society, the research team shows that both Npas4 and ARNT2 are regulated over the disease course of an animal model of MS: prior to disease onset each are increased, presumably in response to early stressors, yet levels decline with disease onset and are lowest at peak disease. The research team will (1) localize and compare Npas4 and ARNT2 expression in models of MS through disease onset, recovery and progression and importantly, in MS lesions compared to ischemic, infectious, non-inflammatory neurodegenerative Central Nervous System diseases and normal human brain, and (2) reduce and augment the expression of the molecules to identify novel mediators and pathways related to neuroprotection, specifically by studying the many downstream factors and proteins that Npas4 and ARNT2 may influence, including when pairing with other partners in biology and disease.

Potential Impact: Further understand key genes/molecules that protect against pathogenic processes in MS to develop novel therapeutics.

Project Status: In Progress

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