Caricamento
Ebri.it



Marco Feligioni

Neuronal Cell Signaling

In the laboratory of "Neuronal Cell Signaling" we are interested to investigate the molecular changes that regulate the onset and progression of several neurodegenerative diseases.

Through molecular and cellular biology techniques we study presynaptic mechanisms of neurotransmitters release and the involvement of NMDA receptors in physiological and pathological conditions.

Moreover, we study post-translational modifications (PTMs) and in particularly we are interested in understanding how SUMOylation is involved in the onset and progression of neurodegenerative diseases.

 

We are currently working on two major projects:

 

1. NMDA receptor and presynaptic role of JNK proteins.

Activation of c-Jun N-terminal kinase (JNK) signaling pathway is a critical step for neuronal death occurring in several neurological conditions. JNKs can be activated via receptor tyrosine kinases, cytokine receptors, G-protein coupled receptors and ligand-gated ion channels, including the NMDA glutamate receptors. While JNK has been generally associated with postsynaptic NMDA receptors, its presynaptic role remains largely unexplored. Our laboratory will investigate the presynaptic role of JNKs and its scaffolding partners in controlling NMDA-dependent glutamate release.

 

2. The role of SUMOylation in various neurodegenerative disorders.

Post-translational modifications (PTMs) are cellular mechanism that finely regulates protein target function, localization, aggregation and degradation.

Specifically, we work on protein SUMOylation to understand its role at the onset and progression of various neurodegenerative diseases.

- Alzheimer's disease (AD). Nowadays it is know that many AD-related proteins also involved in the onset of this disease, such as APP, Tau, GSK3b, BACE1, etc., undergo SUMOylation.

Although this knowledge, the role of SUMOylation at the onset of the disease is not elucidated yet. Therefore, our lab is interested in studying  the SUMOylation involvement in synaptic damage ('Synaptopathy') which is recognized as primer neuronal damage at the beginning of Alzheimer's disease.

Our lab is moreover involved in analyzing blood samples (plasma and cells), cerebrospinal fluid (CSF) of patients affected of Alzheimer's and ALS / FTD trying to find a correlation between these pathologies and the detected variations of sumoylation in these biological fluids. We also analyze autopsy AD brain samples in which we protein SUMOylation levels.

- Sclerosis Amyotrophic Lateral (ALS). Even in this pathology it is known that many important proteins are SUMOylated such as SOD1, fused in liposarcoma (FUS), CTE (COOH terminus of EAAT2) (C-terminal fragment proteolytic glutamate transporter 2).

Indeed, our lab is engaged to study whether the Transactive response DNA-binding protein 43 (TDP43) could be a new SUMO target and eventually which are the effects of this modification. Indeed, the malfunction of this protein is also important in the frontotemporal dementia (FTD).