DNA damage and neurodegenerative diseases: a talk with Claudia Magrin and Martina Sola

Claudia Magrin and Martina Sola are two researchers in neuroscience and PhD students at USI. They both work at the Laboratory for biomedical neurosciences of the Ente Ospedaliero Cantonale, in the research group led by Dr. Paolo Paganetti. They are currently working on a study on the relationship between Tau and P53 proteins in response to DNA damage, published in Communications Biology, one of Nature’s scientific journals. to celebrate this important milestone we turned to the two researchers to find out more about their path and their studies in the laboratory.

The two researchers attended the University of Insubria in Varese, with a specialisation for Martina in Biomedical Neuroscience and for Claudia in Molecular and Industrial Biotechnology. Their passion for neuroscience brought them together and led tem to Ticino for an internship at the laboratory in " Neurodegeneration " directed by Dr. Paolo Paganetti: a chance to combine practical experience with theoretical knowledge thanks to their attendance at the USI’s doctoral school in neuroscience. "Being part of this laboratory was an opportunity to further our passion for neuroscience and investigate a world that is still largely unknown. The passion and daily dedication to research of our tutors, Paolo Paganetti and StÚphanie Papin, and of the whole team is truly contagiuos: this is our job but most of all a vocation that leads us in our fight for the future," explain Claudia and Martina.

Their recent laboratory study deals with DNA damage. Cells are constantly exposed to DNA damaging insults, which can be caused by natural or external factors such as chemicals (pesticides) or UV rays. How do cells react to such damage? "They have developed a complex cells developed a complex molecular response (molecular machinery) that blocks cell separation in an attempt to repair this damage. If this is not possible, it guides the cell to different fates such as programmed cell death (apoptosis) or senescence," explain the researchers. DNA damage causes mutations that can lead to diseases such as cancer and neurodegenerative diseases such as Alzheimer’s disease.

The study to be published in Communication Biology deals in particular with a group of diseases called Tauopathies, the causes of which are not yet fully known. "These are characterised by the pathological deposition of the Tau protein in neurofibrillary tangles. One of the main risk factors is ageing, mainly characterised by an accumulation of DNA damage". In this context, the study carried out in the laboratory shows that Tau influences the DNA repair process and is able to act as a "balance" between two different cellular destinies such as apoptosis or senescence. "After DNA damage - continue Claudia and Martina - the presence of Tau leads to an increase in apoptosis while the absence leads instead to an increase in senescence. The most interesting aspect that we have highlighted is that this choice is regulated through the modulation of a protein, P53, known as the ’guardian of the genome’ and mutated in most human tumors".

The results of the study thus provide indications of potentially common pathways in neurodegenerative diseases and cancer. For Martina, the focus is now on understanding the mechanism of action between Tau, P53 and the fate of these cells subjected to DNA damage; for Claudia, the focus is instead on investigating in detail this possible relationship between neurodegenerative diseases and cancer, in particular by investigating the role of Tau in the development of tumors and in modulating the aggressiveness of these devastating diseases.

The article, published in Communicatios Biology, is available at the following : www.nature.com/comms­bio/