Researchers know that the loss of neurons and their axons is responsible for disability in multiple sclerosis (MS), and inflammation associated with immune cells is thought to be implicated in this process. But to truly understand how the brain’s cells are affected by oxidative stress, researchers led by Dr. Jacqueline Quandt have been looking closely at the mechanisms behind this immune-mediated degeneration. Recently, with the support of the MS Society of Canada and a cadre of local philanthropists, Dr. Quandt has been able to look at parts of the neuronal network in models of MS in greater detail than ever before.
Dr. Quandt and her team, including Pierre Becquart and graduate student Tissa Rahim, have identified a neuroprotective protein that, when lost in an inflammatory setting, may act as a switch between disease progression and processes of repair in MS. The researchers examined the role of ARNT2 (also known as aryl-hydrocarbon receptor nuclear translocator 2), a protein that is responsible for maintaining healthy neurons. ARNT2 is associated with neural growth and development; when the protein is lacking, the brain does not develop normally and results in birth defects and shorter lifespans. ARNT2 is known to be an important contributor to the survival of cells, but its role in central nervous system diseases like MS has not been well understood.
Dr. Quandt’s team evaluated ARNT2 levels in mouse models of MS across the disease course, and found that at the peak of disability, up to 80 per cent of the protein was gone in spinal cord neurons. They also found that ARNT2 expression is tied to brain-derived neurotrophic factor (BDNF), a protein that also supports brain cell survival and growth; . Recovery is associated with the return of ARNT2 expression.
