Read About This Cover and Article
From November 26, 2014 Issue
Lucia Notterpek, Ph.D., the William T. and Janice M. Neely Professor and Chair of the Department of Neuroscience at the University of Florida College of Medicine, recently published results from a noteworthy study performed by her and her research team in the November 26, 2014 issue of the Journal of Neuroscience, a premier neuroscience journal.
The research detailed in this article titled “PMP22 is Critical for Actin-Mediated Cellular Functions and for Establishing Lipid Rafts”, was supported in part by the Facial Pain Research Foundation and Tom and Suzie Wasdin. The Journal of Neuroscience recognizing the quality of this study and of the results obtained, selected an image from this article for the cover of this issue.
The mission of the Facial Pain Research Foundation (FPRF) is to develop a translational (i.e., fundamental discovery to clinical application) research continuum dedicated to identifying critical molecular and cellular mechanisms responsible for causing neuropathic facial pain, to be followed by developing groundbreaking therapeutic strategies that will cure or permanently stop the pain of trigeminal neuralgia (TN) and other related neuropathic pain syndromes.
The experiments described in Dr. Notterpek’s recent article in the Journal of Neuroscience are a superb example of an experimental approach from the fundamental discovery side of research. Its relevance to the mission of the FPRF is based on the idea that TN is thought to occur when the insulating myelin sheath of the trigeminal nerve is lost or damaged (demyelination) by the pulsations of an overlying blood vessel.
Myelin is a multi-layered membrane which is made up of specific lipids and proteins. Due to its molecular composition, myelin functions as an insulating material in the nervous system. Myelin wraps around axons in both the peripheral (PNS) and central (CNS) nervous systems forming a myelin sheath which is instrumental in maintaining the normal conduction velocity in nerves.
Therefore, an intact myelin sheath is essential for the proper functioning of the nervous system. Peripheral myelin is derived from and maintained by Schwann cells. How these lipids and proteins are processed and maintained in myelin-forming Schwann cells is not fully understood but is a major focus of Dr. Notterpek’s research as exemplified by the study described in her recently published manuscript.
Dr. Notterpek focuses her research efforts on discovering the role of a specific Schwann cell gene, peripheral myelin protein 22 (PMP22), in the development and maintenance of myelin. Specifically, the experiments described in this recent article were directed at assessing how cholesterol, the major lipid in myelin, interacts with PMP22 to form a stable myelin sheath. Dr. Notterpek’s findings indicate that PMP22 is most likely a cholesterol binding protein that is critical for myelin stability as demonstrated by the profound myelin abnormalities seen in mice whose PMP22 has been genetically removed (i.e., PMP22 knockout mice).
Also, cholesterol supplementation of cultures derived from these PMP22 knockout mice corrects myelin abnormalities which suggest that they are directly linked with cholesterol deficiency of the plasma membrane (i.e., the outer membrane of most cells). Dr. Notterpek’s results support the existence of a novel but until now undiscovered role for PMP22 in the linkage of the cytoskeleton (cell’s internal structural support system) with the plasma membrane. In this scenario, the newly discovered role of PMP22 is to regulate the cholesterol content of lipid rafts (i.e., membrane microdomains that serve as organizing centers for the assembly of a number of molecular species). Consequently, loss of or the malfunctioning of PMP22 can result in the myelin sheath becoming unstable, and therefore becoming more susceptible to damage and demyelination by an overlying pulsating blood vessel, such as has been proposed to cause TN.
Thus, research studies such as this one performed by Dr. Notterpek and her team, have the potential to provide critical new information for the discovery of effective therapies for TN and other more wide spread demyelinating disorders of the nervous system such as multiple sclerosis (MS).