Regulation of D-amino acids catabolism

PI: Silvia Sacchi and Loredano Pollegioni

 

Participants:

Giulia Murtas, Valentina Rabattoni, Gianluca Molla

Publications:

 

Fundings:

Not funded

Collaborations:

  • Marco Nardini (Dept. of Biosciences, University of Milan, Milan, IT)

  • Leila Birolo (Dept. of Chemical Sciences, University of Naples, IT)

  • Emilia Pedone (Institute of Biostructure and Bioimagine, Naples, IT)

D-amino acid oxidase (DAAO) and D-aspartate oxidase (DASPO) respectively degrade D-serine (D-Ser) and D-aspartate (D-Asp), which in the brain are crucially involved in synaptic plasticity through the modulation of NMDA receptors. Controlling their levels is therefore extremely important for essential cognitive functions such as learning and memory.

In this regard, despite DAAO and DASPO key role, little is known about the regulation of their levels and activity. In the past, we unveiled that human DAAO is inactivated by a regulatory protein (pLG72) and is degraded both by the enodosomes/lysosomes system and the proteasome, upon ubiquitination. More recently, we focused on human DASPO (following the resolution of its 3D structure), its different isoforms and their degradation pathway, as well as on post-translational modifications that could affect the functionality of both enzymes at the cellular level. These studies are aimed at the understanding the complex molecular mechanisms controlling D-Ser and D-Asp brain content under physiological and pathological conditions.

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