Sodium-calcium exchanger (NCX) and ion channels: pivotal elements leading to axonal damage in peripheral nerves? (IonNerve project)

Abstract 

The project will investigate mechanisms leading to the development of peripheral neuropathies (PNs). These can have many different causes: genetic, metabolic, toxic, dysimmune. PNs can impair strength, sensation and involuntary functions (e.g. control of the gastrointestinal tract) in affected patients. In the majority of cases there are no treatments other than symptomatic ones; this is partly due to incomplete knowledge of the damage mechanisms. The project will investigate a possible mechanism common to all these different conditions, with the aim of better defining the cascade of events leading to axonal damage. The objective of the project is to verify the role of a particular molecular family, sodium/calcium exchanger (NCX), as the final and pivotal element in a chain of pathological events. We will therefore verify whether by modulating this specific family or some upstream targets respect to it, it is possible to prevent axonal damage and, consequently, in a future and translational perspective, offer (a) new treatment option(s) for affected patients. We aim at laying the foundations for a better understanding of the mechanisms of axonal damage shared by different conditions that lead to the development of PNs. Considering that 2-3% of the world population is affected by PNs, a strong biological rationale could therefore be provided for innovative therapies for these patients.