Ricerc@Sapienza

Lipid rafts have been identified as further actors of the autophagic process. Autophagy is a ubiquitous intracellular degradation pathway whose levels need to be tightly controlled to secure cell homeostasis. Alterations in lipid rafts components have been hypothesized to contribute to the loss of neural function and potentially to the cell death/cell survival or autophagy balance associated with neurodegeneration (ND). Lipid rafts have been also identified as subdomains on mitochondria-associated membranes (MAMs) proposed as tethering sites between the endoplasmic reticulum (ER) and mitochondrial membranes. The membrane scrambling between ER and mitochondria appears to play a critical role in the earliest steps of autophagy. In fact, this process acts at basal levels to maintain a continuous and effective intracellular clearance but it may also be induced under stress conditions. It has been hypothesized that alteration in MAM's function leads to several human disorders, and in particular can contribute to the loss of neural function and potentially to the cell death associated with ND.
Recently, we clarified the protective role of endogenous neuroglobin (NGB) against ND and its relocalization into the mitochondria lipid rafts. Thus, studying the autophagic machinery during stress condition, this research is aimed to evaluate if the protective role of NGB overexpression may depend on autophagy activation MAM raft-like microdomains mediated.

Thus, this research program is divided into 4 main objectives:
1. Proteomic analysis in neuroblastoma cells overexpressing NGB;
2. Analysis of NGB interaction with MAM raft-like microdomains in neuroblastoma cells after stress induction;
3. Evaluation of NGB MAM-association during autophagy activation;
4. Analysis of NGB neuroprotection using "in vitro" models.
These data could provide new insight on the role of NGB in neuroprotection and/or in the identification of novel pharmacological targets in the control of cell fate.