AHA MCA Project Title
Synapse-to-nucleus Signalling in Alzheimer’s Disease
Who she is
In 2001, Elena Marcello obtained her Master degree in Pharmaceutical Biotechnology (summa cum laude) at the University of Milan, Italy, and in 2002, at the same University, she received her Postgraduate Master degree in “Advanced technologies applied to neurodegenerative disorders”.
In 2006 she completed the PhD in “Pharmacology, Pharmacotoxicology and Pharmaceutical Biotechnology”, at the University of Milan, Italy. During the PhD she was awarded of a short-term fellowship provided by the Italian Society of Pharmacology to visit Prof. Elly Hol lab, at the Netherlands Institute for Neuroscience, Amsterdam (Netherlands).
In 2007 she was awarded “The Dargut and Milena Kemali specialisation scholarship in the field of Basic and Clinical Neurosciences” to join the Center for Applied medical Research (CIMA) in Pamplona (Spain) as post-doctoral fellow in the group of Dr. Isabel Perez-Otano. As part of the European project cPADS, she worked as a Marie Curie fellow in France in 2011 to develop cell permeable peptides as a drug delivery system. In 2012, she was appointed assistant professor of pharmacology at the University of Milano. Since 2019 she has been affiliated as associate professor of pharmacology at the University of Milan.
What she does
Elena Marcello strongly believes that the development of successful strategies for the treatment of Alzheimer’s Disease (AD) will rely on scientific breakthrough discoveries of the initial steps triggering AD pathogenesis cascade. This is the reason why, the main goal of her research activity is to understand the molecular mechanisms implicated in AD synaptic failure, one of the earlier events in AD pathogenesis.
She aimed at placing the primary mechanism of AD pathogenesis, i.e. the amyloid cascade, in the synaptic frame. Her research described the trafficking mechanisms regulating the activity of the enzyme ADAM10, that prevents the generation of amyloid-b peptide, at the synapse. She disclosed a physiological mechanism according to which synaptically regulated ADAM10 activity is positioned to modulate synaptic functioning and amyloid-b peptide production. She found that this pathway is altered in AD and she developed tools able to target ADAM10 trafficking to restore its activity in AD synapses in order to ameliorate synaptic failure and cognitive decline in AD.
Data of Elena Marcello’s group highlight how the knowledge of specific alterations contributing to AD synaptic failure can provide new pharmacological targets to restore synaptic plasticity.
News from the Lab
Recently, Elena Marcello group has characterized the function of CAP2, an actin-binding protein that controls cofilin translocation to dendritic spines. This mechanism is critical for the synaptic plasticity-induced remodeling of spine morphology and is specifically affected in AD hippocampus. CAP2 is downregulated in AD and Marcello group is investigating whether restoring CAP2 levels can rescue cytoskeletal abnormalities and ameliorate cognitive defects in AD. In addition, Marcello group is currently exploring the role of brain metabolic pathways during neurodevelopment and in AD pathogenesis. Thanks to the AHA MCA award, Elena Marcello will investigate the synaptonuclear signaling role in mitochondria dysfunction and synaptic failure in AD.