Merlin: the wizard of nerve repair

 

The Answer: This new research on understanding the mechanism of nerve repair can potentially treat peripheral nerve damage.

(The question to this answer will be revealed at the end of this article. No cheating!)

“Everyone should know this stuff” level

There is a disorder that affects about 20 million people in the US, causing symptoms such as numbness, muscle weakness, and oversensitivity, and in some cases even burning pain, paralysis, and organ dysfunction. In the worst cases, this disorder can also lead to breathing difficulties and organ failure. This disorder is called peripheral neuropathy and it is caused by damage to the peripheral nervous system, the system that transmits information between the central nervous system and the rest of the body. (Peripheral Neuropathy, n.d.).

In the video above this article, I talked more in depth about the function of the nervous system, specifically the peripheral nervous system, and how one disorder can result in such a variation of symptoms. However, in the following paragraphs, I will discuss the process of nerve regeneration further in depth as well as a recent study about a protein called Merlin that plays an essential role in nerve repair.

After nerve damage is sustained, nerve regeneration occurs naturally. The process begins with Wallerian degeneration. During degeneration, the axon, which is the part of a neuron where electrical impulses are conducted away from the nerve’s cell body, starts to degenerate (“Trauma and Wallerian,” n.d.). The purpose is to clean the site of the nerve damage in preparation for regeneration. Another type of cell, Schwann cells, is a key player. As I mentioned in the video, Schwann cells wrap around axons and insulate them, creating the myelin sheath. These cells clear out the remaining debris and speed up the process of repair. Schwann cells then grow to form Bands of Bünger, which guide the regrowing axon to grow where it is supposed to grow (Burnett & Zager, 2004). Doesn’t this sound like no treatment is needed because these peripheral nerve cells can repair themselves and everything will be fine?

Although this may true, the regeneration does not happen immediately and not many therapeutic relief options available, so searching for treatment options to quicken the process is ideal In addition, there are some cases of permanent nerve damage. Researchers at the University of Plymouth conducted a study that explored the process of regeneration more deeply. They investigated what role Merlin plays in the development and function of the peripheral nervous system, and found a pathway that it regulates involved in nerve damage repair. With this new information, they were able to isolate some mechanisms that prevent peripheral nerves from regenerating. Hopefully, in the future, they can develop effective therapies that will help produce nerve repair when it may not have been an option before (University of Plymouth, 2017).

“For geniuses only” level

Merlin uses its magic to regenerate nerves. In a recent study, David Parkinson and his colleagues at the University of Plymouth investigated what role Merlin plays in the development and function of the peripheral nervous system (Short, 2017).  The magic of Merlin not only regenerates nerves but also controls cell development. Quite a few signaling pathways depend on Merlin for controlling cell shape, cell growth, and cell adhesion. Another job Merlin has is to suppress tumors by stopping certain cells from growing uncontrollably. Without Merlin, various nervous system tumors may form in Schwann cells. (“NF2 Gene,” 2017).

The scientists in the University of Plymouth lab used conditional knockout mice that lacked merlin to see what it does. During myelination, the peripheral nerves actually developed pretty normally. However, other studies have proposed that PNS regeneration and PNS development are distinct. Therefore, Parkinson and his colleagues with Thomas Mindos examined how their mice responded to peripheral nerve injury. The mice lacking Merlin were not able to recover from the damage. On the other hand, wild-type mice could recover within three weeks. When the myelin of the Merlin-deficient Schwann cells was lost, they couldn’t become Bünger cells, which are cells that help with the regrowth. The reason for this was the Schwann cells failed to regulate a transcription factor called cJun and were then unable to produce neurotrophins. Neurotrophins are proteins that are growth factors, and help cells survive, differentiate, or grow. The cells in turn then excessively recruited macrophages (Short 2017).

According to Parkinson, the loss of Merlin turns the encouraging environment for regeneration into a hostile, inflammatory environment. Merlin regulates a certain pathway that shields it from regeneration defects. The lack of Merlin allows other proteins to prevent the neuron from regenerating. Merlin is like a wizard that blocks the angry dragon from further damaging the castle, while at the same time allowing the Schwann soldiers to repair the damage that has already been done. Parkinson and his colleagues are now searching for additional targets on the pathway, or if following the analogy: underlings of the dragon. Hopefully, those findings could lead to more research in the therapeutic implications of PNS damage. Since PNS repair can be very slow, targeting this pathway may boost the regenerative process sot that it can be completed sooner (Short, 2017).

 

Fact 1: Peripheral neuropathy can be caused by Types 1 and 2 diabetes, which may explain why diabetic patients may frequently damage their feet and hands because of the lack of sensation (University of Plymouth, 2017).

Fact 2: Pain fibers conduct nerve impulses 2 miles per hour (Haseltine, 2015).

Fact 3: There are more than 100 types of peripheral neuropathy and each one has its own symptoms (Peripheral Neuropathy, n.d.).

The Question: How is the discovery of Merlin’s role in regenerating nerves important?

Works Cited

Burnett, M. G., & Zager, E. L. (2004). Pathophysiology of Peripheral Nerve Injury: A Brief Review. Retrieved February 15, 2017, from MedScape website: http://www.medscape.com/viewarticle/480071_5

CrashCourse. (2015, March 30). Peripheral Nervous System: Crash Course A&P #12 [Video file]. Retrieved from https://www.youtube.com/watch?v=QY9NTVh-Awo

Haseltine, E. (2015, September 24). [Four Fun Facts About Your Peripheral Nervous System]. Retrieved February 15, 2017, from Psychology Today website: https://www.psychologytoday.com/blog/long-fuse-big-bang/201509/four-fun-facts-about-your-peripheral-nervous-system

Hasudungan, A. (2014, December 8). Neurology – Nerve Damage and Regeneration [Video file]. Retrieved from https://www.youtube.com/watch?v=OKr-9WJTHME

NF2 gene. (2017, February 7). Retrieved February 15, 2017, from Genetics Home Reference website: https://ghr.nlm.nih.gov/gene/NF2#

Peripheral neuropathy fact sheet [Fact sheet]. (n.d.). Retrieved February 15, 2017, from National Institute of Neurological Disorders and Strokes website: https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Peripheral-Neuropathy-Fact-Sheet

Short, B. (2017). Merlin weaves its magic on peripheral nerve repair. The Journal of Cell Biology, 216(2). Retrieved from http://jcb.rupress.org/content/early/2017/01/27/jcb.201701082

Trauma and Wallerian Degeneration. (n.d.). Retrieved February 15, 2017, from http://missinglink.ucsf.edu/lm/ids_104_cns_injury/response%20_to_injury/walleriandegeneration.htm

University of Plymouth. (2017, January 30). Paving the way for peripheral nerve damage repair. ScienceDaily. Retrieved February 14, 2017 from www.sciencedaily.com/releases/2017/01/170130092119.htm

University of Wisconsin-Madison. (2016, September 16). Study finds a key to nerve regeneration. ScienceDaily. Retrieved March 1, 2017 from www.sciencedaily.com/releases/2016/09/160916132053.htm

University of Wisconsin-Madison. (2016, September 16). Study finds a key to nerve regeneration. ScienceDaily. Retrieved February 14, 2017 from www.sciencedaily.com/releases/2016/09/160916132053.htm