Fundamental research may help guide approaches to treatment
Knowing that a biological process takes place doesn’t explain the complicated cellular and molecular events that give rise to it.
Consider myelination: the creation of an insulating and protective sheath around nerve fibers. This sheath, made of a substance called myelin, imposes a structural organization that allows for fast, accurate and synchronized electrical transmission of information between nerve cells.
“Although we have a good grasp on the receptors and signaling cascades that promote or inhibit myelination, we still have a very poor understanding on how these pathways crosstalk and are integrated,” says Patrice Maurel, assistant professor in the Department of Biological Sciences at Rutgers University in Newark. “What we are doing in the laboratory is figuring out how this regulation is happening.”
In his work, Maurel is looking at the role of specialized cell adhesion molecules—called Nectin-like (Necl) molecules—in myelination. “These molecules, with their potential ability to form signaling platforms, may be part of this integration mechanism,” he says.
He has studied several aspects of the molecules, including their functional domains, association with proteins in axons nerve fibers and growth factor signaling in myelination. His research seeks to find out both how myelination works normally and how changes happen. That, eventually, may provide scientific evidence for other researchers to develop therapies for diseases marked by myelin loss, such as multiple sclerosis and Charcot-Marie-Tooth disorder, a genetic condition affecting the peripheral nerves.
Maurel also studies how Necl molecules respond after injury. When myelin is damaged or lost, normal messaging between cells in the brain, spinal cord and nerves may be disrupted.
Injury in the peripheral nervous system can regenerate myelin, Maurel notes, but produces sheaths that are shorter and thinner. “In terms of nerve condition, it will be changed, slower. You may have recovery and walk, but lose the fine motor coordination needed for writing,” he says.
Still, that’s better than what happens after injury to the brain or spinal cord. “Very often in the central nervous system, if you have recurring demyelination and remyelination, the axon will degenerate and the neuron cell body from which it comes eventually dies,” says Maurel.
What’s needed, he adds, is to understand the molecular mechanisms that regulate the cycle of loss and remyelination. That could be a long road. “We need to understand the molecular machinery that makes myelin in the first place,” he says.
Maurel believes that Necl molecules may have an impact in cancer research. His laboratory is in an early collaboration with a group at Geisinger Health System in Danville, Pennsylvania, studying neural stem cells derived from patients with glioma and glioblastoma types of brain tumors. He thinks Necl molecules may work in cancer as tumor suppressors, regulating cell growth.
“Necl could become a therapeutic target to prevent migration of these (tumor) cells,” he adds. “They could definitely have an impact broader than remyelination.
Patrice Maurel received a B.S. in natural sciences and a B.S. in biochemistry and molecular biology from Université Paul Sabatier (UPS), the science, technology and health institution of the University of Toulouse in France. He earned his M.S. in pharmacology and molecular toxicology and a Ph.D. in biological sciences-developmental biology, also at UPS. Maurel came to the United States as a post-doctoral fellow in pharmacology at the New York University School of Medicine. While at NYU, he was named an associate research scientist in pharmacology and, later, an associate research scientist and research assistant professor in cell biology. During that time, he won an advanced postdoctoral fellowship award from The National Multiple Sclerosis Society. In 2009, Maurel came to Rutgers University in Newark as assistant professor in the Department of Biological Sciences. The following year, he received the Busch Biomedical Research Foundation Award. He has published numerous journal articles and is a member of The American Society for Cell Biology, Society for Neuroscience and American Society for Neurochemistry.
Selected Publications (Maurel and co-authors)
MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination, Journal of Neuroscience, Vol. 32 (2012)
Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination, Journal of Neuroscience, Vol. 30 (2010)
Primary Schwann cell cultures, Protocols for neural cell culture, 4th Edition (L. Doering ed) Totowa: Humana Press Inc/Springer media. (2010)
Nectin-like proteins mediate axon-Schwann cell interactions along the internode and are essential for myelination, Journal of Cell Biology, Vol. 178 (2007)
Neurofascin interactions play a critical role in clustering sodium channels, ankyrin G and ßIV spectrin at peripheral nodes of Ranvier, Developmental Biology, No. 293 (2006).
Axonal regulation of Schwann cell proliferation and survival and the initial events of myelination requires PI 3-kinase activity, Journal of Neuroscience,Vol. 20 (2000).
Chondroitin sulfate proteoglycans in the developing central nervous system. I: Cellular sites of synthesis of neurocan and phosphacan, Journal of Comp. Neurology, No. 366 (1996).
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