Blocking neuron signaling pathway could lead to new treatments for peripheral neuropathy

January 17, 2017, University of California - San Diego
A colorized electron micrograph depicting mitochondria. These organelles -- the power plants of every cell -- play a critical role in peripheral nerve growth regeneration. Credit: Thomas Deerinck, National Center for Microscopy and Imaging Research, UC San Diego.

Researchers at University of California San Diego School of Medicine, with colleagues at the National Institute of Diabetes and Digestive and Kidney Diseases, the University of Manitoba and St. Boniface Hospital Albrechtsen Research Centre in Canada, have identified a molecular signaling pathway that, when blocked, promotes sensory neuron growth and prevents or reverses peripheral neuropathy in cell and rodent models of type 1 and 2 diabetes, chemotherapy-induced neuropathy and HIV.

The findings are published in the January 17, 2017 issue of the Journal of Clinical Investigation.

Peripheral neuropathy (PR) is a condition resulting from damage to the peripheral nervous system—the vast communications network that transmits information between the central nervous system (brain and spinal cord) and the rest of the body. Symptoms range from numbness, tingling and muscle weakness to severe pain, paralysis and organ dysfunction. An estimated 20 million Americans have some form of PR, which can be a symptom of many diseases, including diabetes and HIV, or a side effect of some chemotherapies.

"Peripheral neuropathy is a major and largely untreated cause of human suffering," said first author Nigel Calcutt, PhD, professor of pathology at UC San Diego School of Medicine. "It has huge associated health care costs."

Previous research has described at least some of the fundamental processes involved in healthy, on-going peripheral nerve growth regeneration, including the critical role of mitochondria—cellular organelles that produce adenosine triphosphate (ATP), the energy-carrying molecule found in all cells that is vital to driving nerve recovery after injury.

In their JCI paper, the researchers looked for key molecules and mechanisms used in sensory and regrowth. In particular, they noted that the outgrowth of neurites—projections from a neuronal cell body that connect it to other neurons—was constrained by activation of muscarinic acetylcholine receptors. This was surprising, they said, because acetylocholine is a neurotransmitter usually associated with activation of cells.

With identification of this signaling pathway, the scientists suggest it is now possible to investigate the utility of anti-muscarinic drugs already approved for use in other conditions as a new treatment for .

"This is encouraging because the safety profile of anti-muscarinic drugs is well-characterized, with more than 20 years of clinical application for a variety of indications in Europe," said senior study author Paul Fernyhough, PhD, professor in the departments of pharmacology and therapeutics and physiology at the University of Manitoba in Canada. "The novel therapeutic application of anti-muscarinic antagonists suggested by our studies could potentially translate relatively rapidly to clinical use."

Explore further: A potential target for peripheral neuropathy treatment discovered

More information: Nigel A. Calcutt et al, Therapeutic efficacy of sonic hedgehog protein in experimental diabetic neuropathy, Journal of Clinical Investigation (2003). DOI: 10.1172/JCI15792

Related Stories

A potential target for peripheral neuropathy treatment discovered

August 3, 2016
Whole exome sequencing has revealed a novel mechanism and potential target for treating peripheral neuropathy, a condition that afflicts millions of people in the United States alone.

Genetic biomarker may predict nerve pain side effects associated with prostate cancer treatment

May 13, 2016
Taxanes are a group of drugs commonly used to treat cancers of the breast, lung, ovary, or prostate, but its use can be limited by significant side effects. Researchers from Moffitt Cancer Center report prostate cancer patients ...

Scientist identifies mechanism underlying peripheral neuropathy

April 14, 2016
Recent research by Sandra Rieger, Ph.D., of the MDI Biological Laboratory identifying the underlying mechanisms of peripheral neuropathy, or nerve damage, has raised the prospect that drug therapies can be developed for the ...

Brain tumours and peripheral neuropathy

March 5, 2013
(Medical Xpress)—Researchers from Plymouth University Peninsula Schools of Medicine and Dentistry are part of an international team which has for the first time identified the role of a tumour suppressor in peripheral neuropathy ...

Study provides new understanding of diabetic peripheral neuropathy

April 11, 2016
A research team from Wayne State University recently published a paper in the Journal of Clinical Investigation that provides a paradigm shift in the understanding of cellular and molecular mechanisms underlying diabetic ...

Recommended for you

Neurons can carry more than one signal at a time

July 18, 2018
Back in the early days of telecommunications, engineers devised a clever way to send multiple telephone calls through a single wire at the same time. Called time-division multiplexing, this technique rapidly switches between ...

Pregnancy history may be tied to Alzheimer's disease

July 18, 2018
A woman's history of pregnancy may affect her risk of Alzheimer's disease decades later, according to a study published in the July 18, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology. ...

Researchers solve mystery of how ALL enters the central nervous system

July 18, 2018
A deadly feature of acute lymphoblastic leukemia (ALL) is its invasion of the central nervous system.

Forty percent of people have a fictional first memory, says study

July 17, 2018
Researchers have conducted one of the largest surveys of people's first memories, finding that nearly 40 per cent of people had a first memory which is fictional.

Protein found to be key component in irregularly excited brain cells

July 17, 2018
In a new study in mice, researchers have identified a key protein involved in the irregular brain cell activity seen in autism spectrum disorders and epilepsy. The protein, p53, is well-known in cancer biology as a tumor ...

New drug target for remyelination in MS is identified

July 17, 2018
Remyelination, the spontaneous regeneration of the fatty insulator in the brain that keeps neurons communicating, has long been seen as crucial to the next big advance in treating multiple sclerosis (MS). However, a lack ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.