Google Play icon

How does neuropathy happen? New research reveals a pathway and a possible therapeutic option

Share
Posted May 15, 2017

Diabetic neuropathy is one of the most common complications of diabetes. While not life-threatening, it affects millions in the U.S. and elsewhere, and leads to limb amputations if left unchecked. But the reasons why metabolic disease can lead to neuropathy, which is damage to the peripheral nervous system, have never been well-understood.

Now, in a paper published this week online in Proceedings of the National Academy of Sciences, researchers at the Hunter James Kelly Research Institute (HJKRI) at the University at Buffalo report on research that illuminates what causes some kinds of neuropathy and may reveal potentially powerful therapies.

Fluorescence microscopy image of in vitro model of myelin sheath (red) formation by Schwann cells around neuronal axons (green). Cell nuclei are blue. Image credit: Keit Men Wong, UB.

The UB researchers have discovered an important metabolic pathway that causes neuropathy when hyperactivated in laboratory animals. They also found they could dramatically cure the mice with a drug called rapamycin, which is already on the market as an immunosuppressant and anti-cancer agent.

The research focuses on the way that cells called Schwann cells drive the formation of myelin in the nervous system. Myelin sheaths protect and insulate axons, the long nerve fibers along which impulses travel between neurons, allowing them to function properly.

In particular, the researchers studied a pathway called mammalian target of rapamycin (mTOR), which plays a key role in regulating cell metabolism, growth and division, as well as aging.

“This pathway is dysregulated in patients with diabetes and other diseases that cause neuropathy,” explained Bogdan K. Beirowski, MD, PhD, principal investigator at the HJKRI and assistant professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB.

Damaged axons

“Myelin sheaths deteriorate in a number of neurodegenerative conditions resulting in axon damage,” said Beirowski, “most prominently in peripheral neuropathies such as diabetic neuropathy that is caused by metabolic tissue imbalances.”

Some other diseases are characterized by an inability of myelin sheaths to properly form during development, and researchers are keenly interested in understanding why this happens. Earlier studies suggested that mTOR may be one of the culprits.

The UB scientists found that when hyperactivated, the mTOR pathway, normally responsible for myelin growth, paradoxically resulted in the Schwann cells’ complete failure to form myelin. The result: The mice lost almost all ability to walk.

The researchers found the inability to form myelin was due to overproduction of Schwann cells.

“There are too many Schwann cells for them to function properly,” explained Beirowski.  “It’s like a crowded room where no one can move around properly because there isn’t enough space and people bump into each other, causing turmoil.”

However, the application of rapamycin caused the Schwann cells to be healed and rejuvenated, allowing for the formation of healthy, new myelin sheaths.

“Within days with this drug, we were able to completely cure the mice of their neuropathy, even in extensively aged animals,” said Beirowski.

Schwann cell plasticity

The finding provides promising evidence of plasticity in Schwann cells, Beirowski said; that is, the ability to regenerate nerves, critical for reversing myelin damage in so many diseases, from muscular dystrophy and multiple sclerosis to Krabbe’s disease and the Charcot-Marie-Tooth family of neurological diseases.

“Our study has revealed central details in the regulation of myelination by the mTOR pathway in Schwann cells,” said co-author Keit Men Wong, a doctoral candidate in the neuroscience program at UB.  “The involvement of this pathway in myelination has been proposed by other scientists, but our work in Dr. Beirowski’s lab for the first time illustrates the relevance of this fascinating molecule for overall Schwann cell development.”

One of the next steps in the research is to determine whether or not the mTOR pathway also is activated in human neuropathies, said Beirowski, who is beginning follow-up studies with Wong and co-author Elisabetta Babetto, PhD, also at the HJKRI.

“We are encouraged by our findings and think that our discoveries could be exploited to regenerate myelin sheaths and nerve structure to help patients with neurological disorders,” he said.

The study was initiated in the laboratory of Jeffrey Milbrandt, MD, PhD, of Washington University in St. Louis, who is co-author on the paper.

Funding for the research was provided by the Muscular Dystrophy Association.

Source: State University of New York at Buffalo

Featured news from related categories:

Technology Org App
Google Play icon
83,316 science & technology articles

Most Popular Articles

  1. Bright Fireball Explodes Over Ontario, Meteorite Fragments Might Have Reached the Ground (August 5, 2019)
  2. Why older people smell the way they do? Japanese have even a special word for it (August 4, 2019)
  3. Terraforming the Surface of Mars with Silica Aerogel? (July 23, 2019)
  4. Swarm Autonomy Tested in Second Major DARPA OFFSET Field Experiment (August 8, 2019)
  5. Dark Matter may Predate even the Big Bang Itself, New Study Suggest (August 8, 2019)

Follow us

Facebook   Twitter   Pinterest   Tumblr   RSS   Newsletter via Email