St. Boniface Hospital Research

Dr. Gordon Glazner
Principal Investigator & Assistant Professor
Division of Neurodegenerative Disorders

In Detail

Cellular biologist Dr. Gordon Glazer is investigating protective mechanisms within the cell. When a neuron is under stress, it fights for survival by increasing the production of certain proteins. The balance that is struck between the death-inducing stress and the production of protective proteins will determine whether the cell lives or dies. The production of these proteins is controlled by transcription factors, and one of the most important of these is NF-kappaB. “NF-kappaB is a stressed-induced anti-stress response,” Dr. Glazner explains. “In neurons, NF-kappaB is always fairly high, which isn’t true of other cells. We believe it is important not just for survival but for function of the neuron itself, so discovering the ways in which outside messengers impact on that can be important for our understanding of how the nerve itself works and, in turn, for our understanding of clinical pathologies which involve neuronal death.”

INVESTIGATING AN END RUN AROUND CELL DEATH

When stressors, such as those caused by stroke or Alzheimer’s disease, activate receptors in the neuron’s endoplasmic reticulum, calcium is released. The release of calcium inside a cell turns on the transcription factor NF-kappaB which acts to protect the cell by stabilizing the calcium. The mechanisms that control the NF-kappaB binding activity are not well understood, and Dr. Glazner’s laboratory is studying the pathways involved.

Dr. Glazer will determine whether the release of calcium increases NF-KappaB binding under stress conditions and whether this activity feeds back and inhibits the further release of calcium. He will also study whether this stress-activated internal calcium release plays a role in apoptosis, or programmed cell death.

In addition, Dr. Glazner will study the role of a recently discovered neurotrophic factor, a protein that facilitates the growth or repair of nerve cells. His studies have found that this factor activates NF-kappaB, and he will continue to investigate it to determine if it works through the feedback pathway.

Understanding how this feedback mechanism works is important clinically. For example, animal models of familial onset Alzheimer’s demonstrate increased release of calcium in their cells, but decreased NF-kappaB. In cardiac disease patients, as well, calcium release is elevated and NF-kappaB is low. In stroke, cells experience a delayed death response for weeks after the initial insult. Further studies of how these feedback pathways work in models of pathenogenisis may point the way toward treatment and preventative measures.

For more information, contact:
Dr. Gordon Glazner
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