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SIB Sezione Giovani/FEBS Junior Sections present Loredano Pollegioni
June 9, 2022 @ 6:00 pm to 7:00 pm CEST
These are the details of the May talk:
Speaker: Prof. Loredano Pollegioni, Università degli Studi dell’Insubria, Italy
Topic: “D-Serine: from unnatural (and negligible) amino acid to (main) neuromodulator involved in relevant human pathologies”
Time: 9 June 2022, 18:00 (CEST)
For more information, see abstract below, the FEBS Network, and Professor Loredano Pollegioni’s webpage.
Professor Loredano Pollegioni
On this talk Prof. Pollegioni will talk about the research path that led to obtaining a drug in the clinical phase bought by Takeda.
Amino acids have an α-carbon that is a stereocenter (or chiral center) since it is connected to four different functional groups. Depending on the spatial arrangement of these four groups, two enantiomers exist: the levorotatory (L-) and the dextrorotatory (D-), which are not superimposable images to each other. At difference from the interest attracted by the L-amino acids, less is known about the biological function of the D-amino acids (D-AAs) in mammals.
D-Serine is the D-AA present at the highest concentration in human brain: it plays a key role in the modulation of N-methyl-D-aspartate receptors (NMDARs) acting as an endogenous co-agonist. In the human CNS, D-serine is produced by the racemization reaction catalyzed by serine racemase and degraded by both serine racemase and D-amino acid oxidase (hDAAO). Abnormal levels of D-serine, due to a defective metabolism or release, have been associated with psychiatric and neurodegenerative diseases (e.g., schizophrenia, bipolar disorder, AD, ALS, etc.). To shed light on the regulation of D-serine level in the brain, we investigated the structural and biochemical properties of hDAAO: this flavoenzyme is regulated by small size ligands, cofactor binding, the interaction with specific proteins and post-translational modifications. These studies are opening new options to modulate NMDAR-mediated neurotransmission in physiological and pathological conditions.