Neurodegenerative Disease: Protecting Neurons and Promoting Their Growth

In neurodegenerative conditions like glaucoma, Alzheimer’s disease, there is injury an to the axon which leads to neuronal impairment and cell death. Axon is a part of neuron which is a long, slender projections that conduct electrical impulses from one nerve to another nerve.

Researchers know that by blocking an enzyme called dual leucine zipper kinase (DLK), neurons can be protected from various neurodegenerative disease models. DLK also blocks axonal regeneration.

No effective methods have been identified till now to modify genes to improve both long-term survival of neurons and promote regeneration.

The research led by the University of California San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health has been published in the journal PNAS

The researchers found another family of enzymes called germinal cell kinase four kinases (GCK-IV kinases). Blocking this enzyme shows a neuroprotective effect while also allows axon regeneration. This makes therapeutic approach for treating some neurodegenerative diseases important.

Senior author Derek Welsbie, MD, PhD, associate professor of ophthalmology in the Viterbi Family Department of Ophthalmology at Shiley Eye Institute, said “We basically 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.”

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A series of screens was conducted by the researchers after creating retinal ganglion cell (RGC) from human stem cells. RGC are a type of neuron in the inner surface of the retina of the eye and they receive the visual information and they transmit this information to the brain.

In the first screen, well-studied chemicals were tested to assess their ability to increase the survival of RGCs. In the second screen the ability of chemicals to promote regeneration was studied.

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Welsbie said, “We then used a machine-learning technique to understand why certain compounds were active while others were not and it identified these key genes. However, you would have predicted that they (like DLK) would have blocked regeneration when inhibited, not promote regeneration. That was definitely a surprise. 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.”

The researchers focused on RGCs as they are interested in optic neuropathies like glaucoma. Glaucoma is a neurodegenerative disease in which there is a progressive loss of RGCs and their axons. This leads to structural and functional damage to the optic nerve which causes visual impairment and blindness.

According to the US Centers for Disease Control and Prevention, 3 million Americans have glaucoma and it is the second leading cause of blindness in the world.

The researchers stated that it’s not yet known whether these findings extend to other neuron types, but they noted that the work suggests strong therapeutic possibilities.

Source-Medindia