Newsletter 05/2020

 The International Meeting on D-Amino Acid Research – IDAR2021 – meeting originally planned in Illinois (USA) in June 2021, has been postponed to 2022. The “D-amino acid community“ is willing to thank the local organizer Jonathan Sweedler for all his efforts in this difficult moment. All news will be published by this Newsletter.

Jean-Pierre Mothet is a new member of Academia Europea

We are really pleased to announce that Jean-Pierre Mothet, an estimated member of our International Scientific Committee, has recently been elected member of the Academia Europea (Academy of Europe) in the section “Physiology & Neuroscience”. The Academia Europea was founded in 1988, on the initiative of several national academies in Europe, and it is the only continent-wide Academy with individual membership from council of Europe states and from other nations across the world. For more information, www.ae-info.org

This has been a very fruitful year for Jean-Pierre, since starting from 2020 he has been also appointed as a member of the Editorial board of Neuropharmacology and as a Review Editor for Frontiers in Cellular Neuroscience.
Congratulations to Jean-Pierre for these prestigious assignments.

 Do you have news concerning the D-amino acids field to announce? Is there a relevant published paper to mention? Write us and take the advantage of this bimonthly Newsletter

• Genomic plasticity of pathogenic Escherichia coli mediates D-serine tolerance via multiple adaptive mechanisms

O’Boyle N, Connolly JPR, Tucker NP, Roe AJ.
Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22484-22493. doi: 10.1073/pnas.2004977117

The authors have explored the adaptation of E. coli EHEC to D-Ser and its consequences for pathogenesis. The isolation of multiple mutants (whose growth was not compromised in the presence of D-Ser) and a combination of whole-genome sequencing and transcriptomics, allowed to show that tolerance could be attributed to disruption of one of two D-Ser transporters and/or activation of a previously nonfunctional D-Ser deaminase. Notably, that disruption of a single transporter, CycA, was sufficient to completely overcome the repression of type 3 secretion system activity normally associated with exposure to D-Ser represents a novel mechanism by which evolution could drive a pathogen to colonize new niches. MORE

ROLE OF D-AAs:

• D-Amino acids in mammalian endocrine tissues

Chieffi Baccari G, Falvo S, Santillo A, Di Giacomo Russo F, Di Fiore MM. Amino Acids. 2020 Sep 15. doi: 10.1007/s00726-020-02892-7

D-Aspartate, D-serine and D-alanine are a regular occurrence in mammalian endocrine tissues, though in amounts varying with the type of gland. This review reports the current knowledge of physiological roles of D-amino acids in endocrine tissues. D-Aspartate is known to act at all levels of the hypothalamus–pituitary–testis axis, playing a key role in reproductive biology in several vertebrate classes. D-Asp has been also immunolocalized in insulin-containing secretory granules in INS-1 E clonal β cells and is co-secreted with insulin by exocytosis. D-Ala immunolocalizes in pituitary ACTH-secreting cells and pancreatic β-cells suggesting that it may participate in blood glucose regulation in mammals. Furthermore, by modulating insulin secretion, D-Ser probably participates in the control of systemic glucose metabolism by modulating insulin secretion. MORE

• D-Serine in physiological and pathological brain aging

Ploux E, Freret T, Billard JM. Biochim Biophys Acta Proteins Proteom. 2020 Sep 17:140542. doi: 10.1016/j.bbapap.2020.140542. Epub ahead of print. PMID: 32950692

Among aging-induced impairments, those affecting cognitive functions certainly represent one the most major challenge to improve elderly quality of life. Because of its relevant function for brain functional plasticity, the NMDA receptor has gathered much interest, especially the activation due to the binding of the co-agonist D-serine. This review presents the most recent information indicating how D-serine could contribute to mechanisms of physiological cognitive aging and also considers the divergent views relative of the role of the NMDA receptor co-agonist in Alzheimer’s disease. MORE

• Cerebrospinal fluid and serum D-serine concentrations are unaltered across the whole clinical spectrum of Alzheimer’s disease

Nuzzo T, Miroballo M, Casamassa A, Mancini A, Gaetani L, Nisticò R, Eusebi P, Katane M, Homma H, Calabresi P, Errico F, Parnetti L, Usiello A. Biochim Biophys Acta Proteins Proteom. 2020 Sep 5;1868(12):140537. doi: 10.1016/j.bbapap.2020.140537

Cerebrospinal fluid (CSF) D-serine has been proposed as a novel biomarker for Alzheimer disease, reflecting dysfunctional activation of neuronal glutamatergic NMDA receptor. In this study, serum and CSF concentration of D-serine and D-aspartate were determined in a cohort of drugfree subjects encompassing the whole AD clinical spectrum and in a cohort of post-mortem AD and control cortex samples. The authors reported unaltered serum and CSF concentrations of D-serine and D-aspartate in AD patients both during the AD progression and compared to non-demented controls. Similarly, cortical D-serine levels were also unaltered in post-mortem samples of AD patients. This study failed to confirm previous findings indicating the CSF D-serine as a novel biomarker for AD. MORE

• D-Serine ameliorates motor and cognitive impairments in β-amyloid 1-42 injected mice by inhibiting JNK signaling pathway

Liu H, Li S, Yang C, Jia H, Gu Z, Tu X, Tian S, Liu J, Li G, Ma Y. J Chem Neuroanat. 2020 Aug 8;109:101852. doi: 10.1016/j.jchemneu.2020.101852

This study aimed to investigate whether D-serine may ameliorate motor and cognitive impairment in Aβ injected mice by inhibiting JNK signaling pathway. Kunming mice were injected intrahippocampally with Aβ1-42 to build the AD model and then were injected intraperitoneally with saline, D-serine, DAAO), and sodium benzoate for 10 consecutive days, respectively. After D-serine treatment, the abilities of movement and memory of mice were improved, and the clearance rate of Aβ was accelerated. The expressions of GFAP, TNF-α, NMDAR1, p-JNK, p-c-Jun and ATF2 decreased significantly. This study showed that D-serine could alleviate the cognitive impairment of Aβ1-42 injected mice by inhibiting JNK signaling pathway further supporting a role for D-serine on AD. MORE

• Dysfunctional D-aspartate metabolism in BTBR mouse model of idiopathic autism

Nuzzo T, Sekine M, Punzo D, Miroballo M, Katane M, Saitoh Y, Galbusera A, Pasqualetti M, Errico F, Gozzi A, Mothet JP, Homma H, Usiello A. Biochim Biophys Acta Proteins Proteom. 2020 Aug 25;1868(12):140531. doi: 10.1016/j.bbapap.2020.140531

This international collaboration focuses on the autism spectrum disorders (ASD). The D-aspartate and D-serine metabolism in the brain and serum of four ASD mouse models was investigated by HPLC and qPCR analyses. The authors found a striking and stereoselective increased D-aspartate content in the prefrontal cortex, hippocampus and serum of inbred BTBR mice, related to a robust reduction in mRNA levels of D-aspartate oxidase, encoding the enzyme responsible for D-aspartate catabolism. This outstanding work calls for a deeper investigation of D-amino acids in the etiopathology of ASD and related developmental disorders. MORE

• D-Amino acid oxidase deficiency is caused by a large deletion in the Dao gene in LEA rats

Shimizu Y, Ishii C, Yanobu-Takanashi R, Nakano K, Imaike A, Mita M, Hamase K, Okamura T. Biochim Biophys Acta Proteins Proteom. 2020 Sep;1868(9):140463. doi: 10.1016/j.bbapap.2020.140463

Previous studies indicated that LEA rats lacked DAO activity, and levels of D-Ser and D-Ala were markedly increased in their tissues. Sequence analysis identified deletion breakpoints located in intron 4–5 of the Dao gene and intron 1–2 of the Svop gene, resulting in a 54.1-kb deletion. A novel congenic rat strain, F344-Daoldao, harboring the Daoldao mutation was generated from LEA rats delivered onto the F344 genetic background. Compared to the parental F344 strain, in F344-Daoldao rats D-Ala was markedly increased in both cerebrum and cerebellum, D-Ser content was increased in cerebellum but not cerebrum, and D-Ala, D-Ser, D-Pro and D-Leu levels were also elevated in plasma. MORE

• A colorimetric assay method for measuring D-glutamate cyclase activity

Katane M, Motoda R, Ariyoshi M, Tateishi S, Nakayama K, Saitoh Y, Miyamoto T, Sekine M, Mita M, Hamase K, Matoba S, Sakai-Kato K, Homma H. Anal Biochem. 2020 Sep 15;605:113838. doi: 10.1016/j.ab.2020.113838

In mammals, metabolism of free D-glutamate is regulated by D-glutamate cyclase (DGLUCY), which reversibly converts D-glutamate to 5-oxo-D-proline and H2O: this reaction is thought to regulate cardiac function. A simple, accurate, and sensitive colorimetric assay method for measuring DGLUCY activity, based on derivatization of 5-oxo-D-proline with 2-nitrophenylhydrazine hydrochloride was developed. 5-Oxo-D-proline was derivatized with 2-nitrophenylhydrazine hydrochloride in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide as a catalyst to generate the acid hydrazides, whose levels were then determined using a colorimetric method. This will represent a well-suited method to elucidate the relationship among DGLUCY activity, the related metabolites and cardiac function. MORE

• Characterization of dye-linked D-amino acid dehydrogenase from Sulfurisphaera tokodaii expressed using an archaeal recombinant protein expression system

Satomura T, Emoto S, Kurosawa N, Ohshima T, Sakuraba H, Suye SI. J Biosci Bioeng. 2020 Sep;130(3):247-252. doi: 10.1016/j.jbiosc.2020.04.008

A gene encoding a dye-linked D-amino acid dehydrogenase (Dye-DADH) homologue was identified in the hyperthermophilic archaeon Sulfurisphaera tokodaii. The gene was efficiently overexpressed using the thermoacidophilic archaeon Sulfolobus acidocaldarius. The purified enzyme catalyzed the dehydrogenation of various D-amino acids, with D-phenylalanine being the most preferred substrate. This represents the first report on membrane-bound Dye-DADH from thermophilic archaea that was successfully expressed in an archaeal host. MORE

The D-amino acids International Research Center “DAAIR“ has been established in Gerenzano (Varese, Italy) in 2019 with the aim to support and perform scientific research projects and activities on the field of D-amino acids. The Center, located inside the Fondazione Istituto Insubrico Ricerca per la Vita, is aimed to represent a pole of excellence at international level for dissemination and research involving the D-amino acids (Director Silvia Sacchi).

The guiding principle is support the research projects aimed to investigate the involvement of D-amino acids in main physiological processes, from bacteria to humans. The ultimate goal is to actively participate to the elucidation of the mechanisms by which the D-amino acids perform specific functions, and to identify their presence and concentration in different organisms and compartments, also with regards to well-established functional states, with particular emphasis to pathological states. Understand the involvement of D-amino acids in important diseases as a way to set up novel therapeutic strategies.

Contacts: info@d-aminoacids.com;
director@d-aminoacids.com;
www.d-aminoacids.com