A novel comprehensive strategy for the study of the molecular basis of Familial Hemiplegic Migraine 3

Migraine is a particularly severe headache that occurs on one side of the head and affects women (13-20%) more than men (3-14%). Familial Hemiplegic Migraine 3 (FHM3) is a rare genetic disorder that, in addition to a strong headache, can cause aura and hemiparesis. FHM3 is caused by defects in the gene encoding Nav1.1, a channel-protein that transports sodium ions and whose activity is responsible for generating and transmitting the fast electrical signals used by nerve cells to communicate over long distances. Mechanisms that determine the onset of FHM3 are still unclear and for this reason the project is mainly aimed at monitoring the functioning of molecules that play an important role in the pathology. To achieve this information, two complementary strategies will be implemented: on the one hand, we will generate and use transgenic mice carrying one of the genetic defects that cause FHM3 to study the electrical properties of defective nerve cells in the native environment. On the other hand, we will use cell culture lines as heterologous expression systems to detect the functional changes of Nav1.1 protein caused by the presence of the genetic defects that cause FHM3. We expect to progress significantly in the knowledge of the mechanisms that cause FHM3 and in particular to understand what are the specific effects of genetic defects at the basis of the pathology, how the defective channel-protein alters the electrical activity of the nerve cells and how this alteration is related to the onset of symptoms of FHM3.