Breakthrough in "marriage-broker" protein
Scientists at the Montreal Neurological Institute and Hospital -The Neuro, at 苹果淫院 and the 苹果淫院 Health Centre, have made a breakthrough in understanding an important protein that appears to act as a kind of cellular 鈥渕arriage broker.鈥� The protein called Netrin1 brings cells together and maintains their healthy relationships. Netrin1 plays an essential role in the growth of the human organism, directing cell migration and the formation of cell circuits both at the embryo stage and after birth.
The breakthrough came in the form of a mouse embryo model created by Jenea Bin and her colleagues working in the laboratory of Dr. Timothy Kennedy, a researcher at The Neuro specializing in nervous system development. Using genetic technology, his laboratory team removed all of the Netrin1 from the embryo. Mouse models are vital in studying the interactions of proteins.
鈥淔or the past two decades, scientists have been using a model in which most but not all of the Netrin1 was removed. That model found that reduced netrin led to developmental problems. Our new model removed Netrin1 totally, and we saw that the consequent disruption of the nervous system was even greater than suspected,鈥� says Dr. Kennedy, contributing author of the study published in August in the scientific journal, Cell Reports. 鈥淪ignificantly, the embryo died about half way through embryogenesis.鈥�
Netrin1 is expressed by many different cells in the adult nervous system. The new model allows Dr. Kennedy to delete Netrin1 from specific cell types at different stages in the cell鈥檚 development.
鈥淧ast studies have implicated Netrin1 in neurodegenerative diseases like Alzheimer鈥檚 disease, in learning and memory and in synaptic plasticity. Using this new mouse, we can now delete Netrin1 expression from specific cells and determine for which function the cells are creating Netrin1. We鈥檒l be able to identify the specific kind of dysfunction that results from Netrin1 deficit.鈥�
Roads to new therapies
Understanding the role of Netrin1 opens roads to new therapies.
鈥淚t is an incredible genetic tool to have available,鈥� says Dr. Kennedy. 鈥淭he same technique used to delete Netrin1 can also be used to increase Netrin1 expression. If we properly manipulate Netrin1 expression in the adult brain, we might be able to maintain a function that was going to degenerate or recover an already degenerated function.鈥�
The new study also casts doubt on a widely held theory that Netrin1 promotes cell survival. 鈥淥ur research found no evidence of that.鈥�
The study was conducted by Dr. Kennedy鈥檚 trainees, Jenea M. Bin, Dong Han, Karen Lai Wing Sun, Jean-Francois Cloutier and Artur Kania.
The study was supported by a Dr. William J. McIlroy Multiple Sclerosis Society of Canada doctoral studentship, Fonds de recherche du Qu茅bec 鈥� Sant茅 awards (doctoral scholarships, Chercheur Senior award, Chercheur Nationaux award), a Killam Foundation Scholar award, and by grants from the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Reseau Quebecois de recherch茅 sur la douleur, the Canada Foundation for Innovation, Brain Canada, and the W. Garfield Weston Foundation.
Link to paper in Cell Reports: (15)00788-3
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