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Deciphering the Negr1 interacting network in physiological conditions and in psychiatric and neurodevelopmental disorders.

Periodic Reporting for period 1 - PSYNegrT (Deciphering the Negr1 interacting network in physiological conditions and in psychiatric and neurodevelopmental disorders.)

Reporting period: 2021-03-01 to 2023-02-28

Psychiatric and neurodevelopmental disorders affect a large and growing number of people in Europe (48 million, 12% of the population in 2017) and worldwide (970 million, 13.2% of the population in 2017). There are still no therapies for the core diagnostic symptoms of most of these disorders. This is likely due to poor knowledge of the mechanisms underlying their pathogenesis. Obejctive of PSYNegrT was to deepen our knowledge by investigating specific elements involved in brain connectivity. By discoverying new elements that play a pivotal role in the onset of neurodevelopmental disorders we greatly advance our understanding of these disorders. In the long term these discoveries could open new therapeutic paradigms for the treatment of these disorders.
Within this project, I made four principal discoveries: (I) Negr1 is altereted in the brain in neurodevelopmental disorders. (II) Negr1 is responsabile for the development of these disorders, (III) Negr1 interacts with a protein encoded by a gene triplicated in Down Syndrome (IV) Negr1 directly interacts with FGFR2. These results are of high quality, interest and translationability.
The results have been presented to large groups at conferences and used in order to start fruitful collaborations. In addition, I presented part of my work to the “Science is fun!” initiative promoted by the MSCAA
PSYNegrT was conceived in order to advance the understanding of the still elusive pathophysiological role of Negr1 during brain development. The project has achieved most of its objectives . In particular, in agreement with the we: (i) strengthen the relationship between Negr1 and onset of neurodevelopmental disorders providing novel and breakthrough evidence; (ii) collected the first evidence of a direct interaction between Negr1 and FGFR2. These results in the short term greatly advanced our understanding of these disorders. In the long term these discoveries could open new therapeutic paradigms for the treatment of neurodevelopmental disorders.
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