California [US], December 15 (ANI): A recent study led by researchers from the University of California - San Diego, has claimed that injury to axons can lead to severe neurodegenerative conditions and also suggested ways to protect it for encouraging neuron growth.
A paper published in Proceedings of the National Academy of Sciences of the United States of America (PNAS), has discovered the injury to that axons- the long, slender projections that conduct electrical impulses from one nerve cell to another, facilitating cellular communications often leads to many neurodegenerative conditions like glaucoma and Alzheimer.
Researchers know that this injury could result in neuronal impairment and cell death. They have also discovered that inhibiting an enzyme called Dual Leucine zipper Kinase (DLK) appears to robustly protect neurons in a wide range of neurodegenerative disease models, and axonal regeneration.
Until now, there have been no effective methods to modify genes to improve both the long-term survival of neurons and promote regeneration.
A multi-university team led by researchers at the University of California San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health identified another family of enzymes called germinal cell kinase four kinases (GCK-IV kinases) whose inhibition is robustly neuroprotective, while also permitting axon regeneration, making it an attractive therapeutic approach for treating at some neurodegenerative diseases.
Senior author Derek Welsbie, MD, PhD, associate professor of ophthalmology in the Viterbi Family Department of Ophthalmology at Shiley Eye Institute said "We figured out that there are a set of genes that, when inhibited, allow optic nerve cells to survive and regenerate,"
"Prior to this work, the field knew how to get these cells to survive, but not regenerate. Conversely, there are ways to promote regeneration, but then the survival was rather modest. Of course, for a successful strategy of vision restoration, you need both and this is a step in that direction."
The researchers conducted a series of screens after first creating retinal ganglion cells (RGC) from human stem cells. RGCs are a type of neuron located near the inner surface of the retina of the eye. They receive visual information from photoreceptors and collectively help transmit that information to the brain.
The first screen involved testing a group of well-studied chemicals to assess their ability to increase the survival of RGCs; the second to measure the ability of chemicals to promote regeneration.
"We then used a machine-learning technique to understand why certain compounds were active while others were not and it identified these key genes," said Welsbie.
They discovered that these genes improved RGC survival, "However, you would have predicted that they (like DLK) would have blocked regeneration when inhibited, not promote regeneration. It highlights one of the advantages of discovery-based science using high-throughput screening: By testing many agents at once, we can find identify overlooked genes that might not have been thought to play a role."
Welsbie and colleagues focused their work on RGCs because they are interested in optic neuropathies, such as glaucoma. "Most people think only about glaucoma in terms of 'eye pressure,'" Welsbie said.
"But eye pressure is only part of the problem. At its core, glaucoma is a neurodegenerative disease characterized by progressive loss of RGCs and their axons, leading to measurable structural and functional damage to the optic nerve, visual impairment, and blindness," he added.
The U.S. Centers for Disease Control and Prevention estimate 3 million Americans have glaucoma. It is the second leading cause of blindness worldwide.
Welsbie cautioned that it's not yet known whether these findings extend to other neuron types, but he noted that the work suggests strong therapeutic possibilities. (ANI)