Published September 11, 2015
A research team led by Richard M. Gronostajski, PhD, professor of biochemistry, has discovered a new way to generate oligodendrocytes. This method has the potential to enhance treatments for brain injury, multiple sclerosis, Alzheimer’s disease and more.
The deletion of a protein needed for early development in the brain fostered growth of cells that generate myelin, the protective coating neurons need to function.
The research, published in Stem Cells and Development, provides new insight into how critical brain cells are generated. It also may lead to improved treatments for brain injury, demyelinating diseases, and brain tumors.
As neural stem cells differentiate into oligodendrocytes, the expression of the protein Nuclear Factor I X (NFIX) decreases, which research shows is an essential step in the normal formation of the myelin-making cells.
Gronostajski explained oligodendrocytes surround neurons, protecting them from damage and speeding along the transmission of electrical signals in the brain.
Thirty years ago, while working in a lab at Albert Einstein College of Medicine, Gronostajski contributed to the discovery of NFI proteins.
His new research demonstrates how complex a role NFIX and other related transcription factors, proteins that turn genes on and off, play in development.
NFIX is required for normal development of the early brain and it’s known that losing NFIX before birth results in a number of rare human diseases, characterized by severe developmental and physiological defects.
However, the new study shows that the loss of NFIX is necessary at a certain point in order for some brain cells to develop normally.
“This paper is about the increase in oligodendrocytes, the myelin-making cells, that we discovered when we deleted NFIX from adult neural stem cells,” explained Gronostajski.
“Producing more oligodendrocytes could help prevent the damage to neurons that occur in MS and other demyelinating diseases, such as Krabbe disease,” said Gronostajski, who directs the Genetics, Genomics and Bioinformatics program at UB and the Western New York Stem Cell Culture and Analysis Center.
“In terms of a treatment, this could lead to the development of a small molecule that could be used to shut off NFIX activity in MS patients, thus promoting the growth of more oligodendrocytes,” he said.
This study and previous ones have found that loss of NFIX could also increase the growth of adult neural stem cells, which, in turn, could generate new neurons in adult animals.
“This could also help us find ways to stimulate new neuron production in diseases where neurons die, such as in Alzheimer’s and Parkinson’s diseases and in spinal cord injury,” explained Gronostajski.
Co-authors from the Department of Biochemistry are:
Other co-authors include:
The work was funded by NYSTEM, the National Health and Medical Research Council and the Australian Research Council Future Fellowship.