Neurodegenerative diseases like Alzheimer’s disease and Glaucoma are characterized by damage to neural axons, thread-like projections that carry electrical impulses from one nerve cell to another. Axonal injury often causes dysfunction of neurons and ultimately the death of axons.
What we know so far about Neurodegeneration
Evidence found by Researchers has shown that dual leucine zipper kinase (DLK) is a key regulator enzyme of progressive neuronal degeneration, the inhibition of which can be a potential approach in the treatment of numerous neurodegenerative conditions. Though it is neuroprotective, it also inhibits axonal regeneration. No effective ways to improve long-term survival and promote the regeneration of axons were available till now.
Read Also: Can Neurons Regenerate? A New Study Says They Can
What research has recently found
On December 14, 2020, in a paper published in PNAS, researchers claimed they had found a new class of enzymes known as germinal cell kinase four (GCK-IV) kinases whose inhibition improves the long-term survival of neurons and also promotes the regeneration of axons. This feature could be of great help in the treatment of some degenerative diseases of neurons through a different modality.
A different approach to finding the Enzyme
Researchers initially used human stem cells to generate Retinal ganglion cells (RGCs). RGCs are a group of neurons situated in the inner surface of the retina that take visual information from the eye and then transmit it to the visual center of the brain.
Researchers performed multiple screenings to test the chemicals. The first screening included well-understood chemicals for assessing the ability of RGCs to survive; the next screening was done to determine if these chemicals can promote regeneration.
Following the screening, the machine-learning technique was used to study the activity of several compounds that later helped identify these key genes.
Researchers were surprised, as DLK only blocked regeneration when inhibited. They also promoted regeneration. Similarly, the adenovirus approach with Genomic editing found the benefit of GCK-IV over DLK in the promotion of regeneration of axons.
Advantages of Discovery-based science
It helps testing several agents at a time, which can be a great help in identifying those unnoticed genes that were not supposed to play any role in the past.
Why were RGCs selected for the study?
Researchers working on the project were quite interested in optic neuropathies like glaucoma. According to what the researchers say, there is a misconception that only eye pressure causes glaucoma. But in fact, it is not just related to eye pressure. Eye pressure is the tip of the iceberg, with a big problem within- a submerged part of the iceberg. At the root level,l glaucoma is characterized by a progressive optic neuropathy resulting in a specific pattern of irreversible visual field defect associated frequently but not invariably with increased eye pressure.
Read Also: Glaucoma Breakthrough: Vision Loss in Mice Restored With Anti Aging Cocktail
What Statistical data says about Glaucoma
Glaucoma is the 2nd leading cause of blindness worldwide. Approximately 3 million Americans are suffering from glaucoma currently.
Is the discovery of these genes of benefit?
As it not only improves long-term neuronal survival. But also promote the regeneration of neurons, which can be of great help in treating several neurodegenerative disorders.
References
Welsbie, D. S., Yang, Z., Ge, Y., Mitchell, K. L., Zhou, X., Martin, S. E., Berlinicke, C. A., Hackler, L., Fuller, J., Fu, J., Cao, L.-h., Han, B., Auld, D., Xue, T., Hirai, S.-i., Germain, L., Simard-Bisson, C., Blouin, R., Nguyen, J. V., … Zack, D. J. (2013). Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. Proceedings of the National Academy of Sciences, 110(10), 4045–4050. https://doi.org/10.1073/pnas.1211284110
