Ricerc@Sapienza

The present work is part of an advanced project that points to characterize the molecular mechanisms of Dimethylfumarate (DMF), recently approved as a treatment for Multiple Sclerosis (MS). The DMF is supposed to exert anti-inflammatory effects, but its therapeutic action is unknown.
Our preliminary data showed that Ferritin uptake in microglia is greatly enhanced by DMF presence: as we proved, this phenomenon is due to a higher Transferrin Receptor expression on microglia surface caused by DMF. This observation could link the recent studies stating iron metabolism dysregulation in microglia of brains in sclerotic patients and the neuroprotective effects that DMF exercises: according to our conjectures, DMF would reestablish the damaged iron internalization by microglia, thus acting both as a neuroprotector and as a regulator of iron metabolism.
The action of this compound seems to be highly specific for Ferritin uptake in microglia: in the proposed research we will focus on the diffusion of ripples that are triggered only by the simultaneous presence of DMF and Ferritin. These ruffles are spherical waves, created by microglia, that spread on the surface of the culture dish from cells somas to a long distance. We think that these waves are due to a Calcium dependent phenomenon: our aim is to confirm this hypothesis.
To do so, we will analyze the dynamics of the ripples by detecting the Calcium levels in microglial cultures through the activity of fluorescent probes. This characterization will be done with a handmade innovative optical setup that we built in order to detect the collective dynamics of Calcium transients in a large area; an automatized software, that we wrote in Matlab, will recognize front waves and quantify their temporal behavior.
In this way, we will use multidisciplinary and complementary techniques to better understand the link between iron dysregulation in microglia and DMF anti-inflammatory properties.