Alterations in D-Amino Acid Metabolism in Psychiatric and Neurological Disorders: 2nd Edition

Dear Colleagues,

As this topic continues to draw scholars' attention and remains scientifically important, we are pleased to announce a second edition of the Special Issue “Alterations in D-Amino Acid Metabolism in Psychiatric and Neurological Disorders”.

All amino acids, except for glycine, have a chiral carbon center that allows for the formation of two stereoisomers that are mirror images of each other. However, despite their potential to exist in both left-handed (L) and right-handed (D) forms, animal organisms exclusively use L-amino acids as building blocks of proteins and intermediates of biochemical processes. In this context, the free D-amino acids identified for the first time between the 1980s and the 1990s in biological tissues of mammals, including humans, were initially considered a by-product of the diet and/or the intestinal bacterial flora. However, the recent discovery of enzymes involved in free D-amino acids biosynthesis, along with the long-established existence of enzymes responsible for selective D-amino acid degradation, have led to the hypothesis that these “unusual” molecules might play a role in the biology of mammals. To date, several D-amino acids have been identified in the mammalian brain and peripheral organs. Among them, D-serine and D-aspartate have been reported to occur in larger amounts and emerge in a time- and tissue-dependent manner. In the central nervous system, D-serine and D-aspartate bind to the N-methyl D-aspartate (NMDA) subtype of glutamate receptors, with the former being a co-agonist at the glycine binding site and the latter a direct agonist at the glutamate binding site. In light of their respective pharmacological abilities, different studies in animal models and humans have shown that these D-amino acids can modulate different NMDA receptor-dependent processes, including synaptic plasticity, brain development and cognition. It is well known that NMDA receptors are also implicated in brain aging, and their dysfunctional activity is relevant to the etiology and pathophysiology of a wide range of psychiatric and neurological disorders, including schizophrenia, autism, depression, addiction, amyotrophic lateral sclerosis, multiple sclerosis and neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Given their neuromodulatory influence on NMDA receptors, different studies have recently evaluated the involvement of D-serine and D-aspartate in some of the above-mentioned disorders, identifying a dysregulated metabolism of these molecules and hypothesizing, in some instances, a potential role as biomarkers or therapeutic agents. These issues, however, are still matter of debate within the scientific community.

Based on this evidence and the still unresolved questions, in this Special Issue, we invite scientists to submit original research articles and review articles exploring the roles of D-serine, D-aspartate and possibly other D-amino acids in the neurobiology and neuropathology of psychiatric and neurological disorders.

Prof. Dr. Alessandro Usiello
Dr. Francesco Errico
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• neurological disorders
• psychiatric disorders
• NMDA receptors
• D-aspartate
• D-serine

• Cellular and Molecular Mechanisms of Neurodegenerative and Neurological Diseases in Biomolecules (8 articles)