Review
Pharmacology & Pharmacy
Anna Pittaluga
Summary: This review summarizes the results from synaptosome studies over the past 40 years, supporting the existence of auto and hetero NMDA receptors controlling the release of transmitters in the CNS of mammals. Additionally, immunochemical studies in isolated nerve endings confirm these functional observations.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Neurosciences
Dolores Piniella, Francisco Zafra
Summary: This article discusses the functions of NMDA-type glutamate receptors (NMDARs) in the central nervous system and their interaction with other endogenous ligands. The activity of NMDARs depends on the coincidental binding of glutamate with other cellular signals and is modulated by allosteric modulators such as zinc and protons. The GlyT1 transporter plays an important role in maintaining glycine concentration in the microenvironment of NMDARs. Although the inhibition of GlyT1 has been investigated as a treatment for schizophrenia, the results from phase III clinical trials have been disappointing. However, further research and the newly published 3D structure of GlyT1 may lead to the design of more effective drugs.
Article
Biochemistry & Molecular Biology
E. Ploux, T. Freret, J-M Billard
Summary: As people age, communication and plasticity between neurons weaken, with NMDAr activation playing a crucial role in brain plasticity. D-serine may contribute to mechanisms of physiological cognitive aging.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Article
Geriatrics & Gerontology
Olayemi Joseph Olajide, Clifton Andrew Chapman
Summary: The study found that Aβ(1-42) can rapidly disrupt glutamatergic transmission in the entorhinal cortex, primarily by affecting molecular levels presynaptically and postsynaptically, and involving concurrent activation of GluN2A- and GluN2B-containing NMDA receptors.
NEUROBIOLOGY OF AGING
(2021)
Article
Neurosciences
Steven O. Devenish, Bryony L. Winters, Lyndsey L. Anderson, Jonathon C. Arnold, Iain S. McGregor, Christopher W. Vaughan, Mary Chebib, Nathan L. Absalom
Summary: The study evaluated the effects of anticonvulsant drugs on recombinant and native glycine receptors, with zonisamide showing positive modulation on glycine receptors and potentially mediating anticonvulsant effects through this action.
Review
Neurosciences
David Stroebel, Laetitia Mony, Pierre Paoletti
Summary: Ionotropic glutamate receptors (iGluRs) are essential for excitatory neurotransmission in the vertebrate CNS and play a major role in learning and memory. Some iGluR subunits do not bind glutamate, but instead bind glycine and D-serine, which have different roles and affinities in various subtypes of glycinergic iGluRs. Glycine and D-serine influence the activity and function of iGluRs, reshaping our understanding of their signaling diversity and complexity in neuropharmacology.
Article
Psychiatry
Barbara Lombardo, Marco Pagani, Arianna De Rosa, Marcella Nunziato, Sara Migliarini, Martina Garofalo, Marta Terrile, Valeria D'Argenio, Alberto Galbusera, Tommaso Nuzzo, Annaluisa Ranieri, Andrea Vitale, Eleonora Leggiero, Anna Di Maio, Noemi Barsotti, Ugo Borello, Francesco Napolitano, Alessandra Mandarino, Marco Carotenuto, Uriel Heresco-Levy, Massimo Pasqualetti, Paolo Malatesta, Alessandro Gozzi, Francesco Errico, Francesco Salvatore, Lucio Pastore, Alessandro Usiello
Summary: The study suggests that D-aspartate plays an important role in neurodevelopment and functioning, and the dysmetabolism of D-aspartate is associated with neurodevelopmental disorders such as schizophrenia. Using a mouse model, the researchers found that early occurrence of D-aspartate can influence neurodevelopment and lead to social recognition memory deficits.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Physiology
M. J. Olivares, A. Flores, R. von Bernhardi, J. Eugenin
Summary: Central respiratory chemoreceptors play a key role in maintaining respiratory homeostasis by sensing CO2 and H+ levels in the brain and activating the respiratory neural network. Glutamatergic neurons and astrocytes in specific brain regions, such as the RTN, contribute to this process by releasing ATP in response to hypercapnia and D-serine and glutamate as gliotransmitters.
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Zhongtang Li, Guanxing Cai, Fan Fang, Wenchao Li, Minghua Fan, Jingjing Lian, Yinli Qiu, Xiangqing Xu, Xuehui Lv, Yiyan Li, Ruqiu Zheng, Yuxi Wang, Zhongjun Li, Guisen Zhang, Zhenming Liu, Zhuo Huang, Liangren Zhang
Summary: A series of furan-2-carboxamide analogues were identified as novel NMDAR-positive allosteric modulators, with FS2921 showing potential antidepressant effects. Compound 32h exhibited increased NMDAR excitability in vitro and significant antidepressant activity, with a favorable PK/PD profile. This study presents a new potential opportunity for discovering new antidepressants through novel NMDAR PAMs.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Roberta de Ceglia, Ada Ledonne, David Gregory Litvin, Barbara Lykke Lind, Giovanni Carriero, Emanuele Claudio Latagliata, Erika Bindocci, Maria Amalia Di Castro, Iaroslav Savtchouk, Ilaria Vitali, Anurag Ranjak, Mauro Congiu, Tara Canonica, William Wisden, Kenneth Harris, Manuel Mameli, Nicola Mercuri, Ludovic Telley, Andrea Volterra
Summary: A subpopulation of astrocytes selectively expresses synaptic-like glutamate-release machinery, actively secretes the transmitter, and is localized to discrete sites in the hippocampus. These specialized astrocytes play important roles in central nervous system physiology and diseases, and may serve as a potential therapeutic target.
Review
Environmental Sciences
Najm Alsadat Madani, David O. Carpenter
Summary: Glyphosate and glyphosate-based herbicides have adverse effects on nervous system function, including increased risk of Parkinson's disease and autism, impaired synaptic transmission through mechanisms such as oxidative stress and mitochondrial dysfunction. In addition, glyphosate-based herbicides alter the gut microbiome, which in turn affects susceptibility to neurological diseases.
ENVIRONMENTAL RESEARCH
(2022)
Article
Neurosciences
Deborah K. Park, Samuel Petshow, Margarita Anisimova, Eden V. Barragan, John A. Gray, Ivar S. Stein, Karen Zito
Summary: This study shows that decreased D-serine levels associated with schizophrenia enhance ion flux-independent NMDAR signaling, leading to destabilized dendritic spines. This hypothesis was tested using the serine racemase knockout mouse model and the results support the hypothesis.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Dayton J. Goodell, Jonathan E. Tullis, K. Ulrich Bayer
Summary: Studies have shown that acute inhibition of DAPK1 blocks LTD in hippocampal CA1 synapses in young mice, while genetic deletion of DAPK1 does not reduce LTD due to a compensatory presynaptic mechanism. Additionally, young DAPK1 knockout mice exhibit reduced basal glutamate release probability, an effect that normalizes with maturation and may prevent a reduction of LTD.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anna Pittaluga, Alessandra Roggeri, Giulia Vallarino, Guendalina Olivero
Summary: Somatostatin plays a role in controlling synaptic transmission efficiency in the central nervous system, mainly by modulating presynaptic glutamate exocytosis or by modulating glutamate receptors that are functionally coupled with somatostatin receptors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Psychiatry
Magdalena Orzylowski, Esther Fujiwara, Darrell D. Mousseau, Glen B. Baker
Summary: Dementia, including Alzheimer's disease, is characterized by progressive cognitive deterioration with profound memory loss. D-serine plays a crucial role in the activation of NMDAR and regulation of learning and memory, making it important for both normal aging and dementia.
FRONTIERS IN PSYCHIATRY
(2021)
Review
Biochemistry & Molecular Biology
Elena Rosini, Loredano Pollegioni
Summary: Oxidases, specifically FAD-containing enzymes such as glucose oxidase, have shown promise in cancer therapy by producing reactive oxygen species in tumors and potentially modulating cytotoxic compound production. Advances in nanotechnologies and protein engineering have improved tumor specificity, making oxidase-based ROS production a mature and applicable approach in clinical settings.
Review
Biochemistry & Molecular Biology
Giulia Murtas, Loredano Pollegioni
Summary: D-amino acids, present in the human body from various sources, play important roles in physiological processes and are increasingly linked to different pathological states. Determining their levels in blood can serve as diagnostic and prognostic biomarkers for multiple disorders, including neurological and psychiatric conditions. Further studies are necessary to standardize and confirm the clinical effectiveness of these measurements.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Elena Rosini, Loredano Pollegioni
Summary: This article presents an optimized workflow for the expression and purification of various human proteins using Chinese Hamster Ovary cells (CHO). The workflow allows for high yield and high quality protein production, and can be completed within 2 weeks. The platform has also been successfully adapted for the production of the receptor-binding domain (RBD) in the SARS-CoV-2 S protein, which is crucial for COVID-19 research.
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Valentina Pirillo, Marco Orlando, Caren Battaglia, Loredano Pollegioni, Gianluca Molla
Summary: Improved variants of PET-hydrolysing enzymes were generated by protein engineering. The F243T variant partially depolymerized PET film, while the S101N/F243T double variant showed higher activity. The highest conversion yield for both variants was obtained at 55°C. The S101N/F243T variant is capable of fully depolymerizing untreated postconsumer PET waste within 3 days at 55°C, making it a more ecofriendly and sustainable process.
Article
Chemistry, Multidisciplinary
Filippo Molinari, Loredano Pollegioni, Elena Rosini
Summary: In this study, an efficient and green process was developed to produce valuable compounds from renewable feedstocks through extraction optimization and genetic engineering of E. coli strain. The optimized whole-cell system demonstrated a sustainable and cost-competitive approach for producing high value-added products from renewable resources.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Valentina Rabattoni, Francesco Marchesani, Giulia Murtas, Silvia Sacchi, Andrea Mozzarelli, Stefano Bruno, Alessio Peracchi, Loredano Pollegioni, Barbara Campanini
Summary: De novo L-serine biosynthesis in mammalian astrocytes involves a linear, three-step pathway that is catalyzed by PHGDH, PSAT, and PSP. The formation of a complex between these enzymes has been observed in human astrocytes and in in vitro experiments.
Review
Biochemistry & Molecular Biology
Giulia Murtas, Loredano Pollegioni
Summary: D-amino acids have been found to play important roles in specific cancer types, including cancer cell proliferation, cell protection during therapy, and as potential biomarkers. More research is needed on the relationship between D-amino acids, their nutritional value, and cancer cell proliferation and survival.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Evan C. Rosenberg, Simon Chamberland, Michael Bazelot, Erica R. Nebet, Xiaohan Wang, Sam McKenzie, Swati Jain, Stuart Greenhill, Max Wilson, Nicole Marley, Alejandro Salah, Shanice Bailey, Pabitra Hriday Patra, Rebecca Rose, Nicolas Chenouard, Simon(e) D. Sun, Drew Jones, Gyorgy Buzsaki, Orrin Devinsky, Gavin Woodhall, Helen E. Scharfman, Benjamin J. Whalley, Richard W. Tsien
Summary: CBD reduces seizures in pediatric epilepsies, possibly by blocking the effects of LPI at synapses and reducing hyperexcitability.
Correction
Chemistry, Multidisciplinary
Filippo Molinari, Loredano Pollegioni, Elena Rosini
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(2023)
Review
Multidisciplinary Sciences
Elena Rosini, Loredano Pollegioni, Gianluca Molla
Summary: In this review, the enantiospecific interaction between proteins and chiral amino acids is explored. The molecular basis of the ability of certain enzymes to discriminate opposite enantiomers is described. The analysis showcases the importance of natural evolution in shaping biological processes.
Review
Chemistry, Physical
Elena Rosini, Filippo Molinari, Davide Miani, Loredano Pollegioni
Summary: Lignin, the second most abundant polymer in nature, has the potential to be a valuable feedstock for the production of value-added chemicals, rather than simply being burnt for energy supply. Recent advancements in systems metabolic engineering have allowed for the design of microbial cell factories that efficiently degrade lignin and transform its products into useful compounds. This review focuses on successful case studies, conducted at the laboratory/pilot scale, that demonstrate the generation of value-added and specialty chemicals, with a particular emphasis on the production of cis,cis-muconic acid, an important building block for plastic materials synthesis. The transformation of this waste stream into a sustainable product portfolio awaits the resolution of economic challenges related to process scale-up.
Article
Biotechnology & Applied Microbiology
Elena Rosini, Marta Boreggio, Matteo Verga, Laura Caldinelli, Loredano Pollegioni, Elisa Fasoli
Summary: The study explores a new cancer treatment strategy by using an external enzyme to convert prodrugs into active anticancer compounds directly in tumor sites. It is found that a D-amino acid oxidase variant with five aminoacidic substitutions (mDAAO) has better therapeutic efficacy than the wild-type DAAO (wtDAAO) in catalyzing the oxidative deamination of D-amino acids. Functionalized multi-walled carbon nanotubes (MWCNTs) with polyethylene glycol (PEG) enhance the activity and cytotoxicity of DAAO, with mDAAO showing higher cytotoxicity at low O-2 concentration.
Article
Pharmacology & Pharmacy
Sara Tengattini, Davide Rubes, Massimo Serra, Luciano Piubelli, Loredano Pollegioni, Enrica Calleri, Teodora Bavaro, Gabriella Massolini, Marco Terreni, Caterina Temporini
Summary: Conjugation via disuccinimidyl homobifunctional linkers is a convenient approach for the synthesis of glycoconjugate vaccines. However, the hydrolysis of these linkers makes their purification challenging, resulting in side reactions and impure glycoconjugates. In this study, the conjugation of 3-aminopropyl saccharides via disuccinimidyl glutarate (DSG) was utilized to synthesize glycoconjugates. Through optimization of purification protocols and conjugation conditions, high sugar-loaded and pure glycoconjugates were obtained, making this approach valuable for the production of well-defined glycovaccines.
Article
Biochemistry & Molecular Biology
Francesco Marchesani, Annalisa Michielon, Elisabetta Viale, Annalisa Bianchera, Davide Cavazzini, Loredano Pollegioni, Giulia Murtas, Andrea Mozzarelli, Stefano Bettati, Alessio Peracchi, Barbara Campanini, Stefano Bruno
Summary: The phosphorylated pathway (PP) in humans converts D-3-phosphoglycerate (3-PG) into L-serine through several enzymes. Genetic defects of these enzymes are associated with serine deficiency disorders (SDDs). This study characterizes different PSAT variants associated with SDDs and non-SDDs and shows that the pathogenetic mechanisms in SDDs are diverse. These findings confirm the importance of PSAT dysfunctions as a cause of SSDs.
Article
Clinical Neurology
Anderson Brito da Silva, Jane Pennifold, Ben Henley, Koustav Chatterjee, David Bateman, Roger W. Whittaker, Abhijit Joshi, Hrishikesh Kumar, Claire Nicholson, Mark R. Baker, Stuart D. Greenhill, Richard Walsh, Stefano Seri, Roland S. G. Jones, Gavin L. Woodhall, Mark O. Cunningham
Summary: For the first time, it has been shown that perampanel has potent antiepileptic action in human FCD brain slices, likely through reducing burst firing behavior. This finding may have implications for the treatment of refractory epilepsy associated with FCD in humans.
Correction
Neurosciences
Lucia Privitera, Ellen L. Hogg, Matthias Gaestel, Mark J. Wall, Sonia A. L. Correa
Article
Neurosciences
Li-Ya Jiang, Guan-Hao Wang, Jing-Jiao Xu, Xiao-Li Li, Xiao-Yan Lin, Xiang Fang, Hong-Xu Zhang, Mei Feng, Chun-Ming Jiang
Summary: This study reveals the importance of LINC00473 in regulating temozolomide (TMZ) resistance in glioblastoma (GB) and its potential mechanism. By regulating the expression of CEBP alpha and MGMT, LINC00473 promotes the formation of chemoresistance. Furthermore, LINC00473 can transfer chemoresistance to adjacent sensitive cells through exosomes.
Article
Neurosciences
Olga Kopach, Tetyana Pivneva, Nataliya Fedirko, Nana Voitenko
Summary: This study found that diabetic animals exhibit severe xerostomia characterized by reduced saliva flow rate, diminished total protein content, and decreased amylase activity. The impaired saliva production in diabetes is associated with reduced and delayed intracellular Ca2+ signals in submandibular acinar cells, caused by malfunctioning mitochondria. Targeting malfunctioning mitochondria may be a potential strategy for the treatment of diabetic xerostomia.
Article
Neurosciences
Nicholas M. Timme, Cherish E. Ardinger, Seth D. C. Weir, Rachel Zelaya-Escobar, Rachel Kruger, Christopher C. Lapish
Summary: This study aimed to assess aversion-resistant drinking behavior in head-fixed mice and explore the relationship between non-consummatory behaviors and aversion-resistant drinking. The results showed that head-fixed mice exhibited heterogenous levels of aversion-resistant drinking and non-consummatory behaviors were related to the intensity of this behavior.
Article
Neurosciences
David R. Maguire, Charles P. France
Summary: Methocinnamox (MCAM) is a novel, long-acting opioid receptor antagonist that effectively decreases fentanyl self-administration and prevents opioid overdose in monkeys. The study demonstrates the potential therapeutic utility of MCAM in the treatment of opioid use disorder.
Article
Neurosciences
Xiang Li, Dan Feng, Shenglu Ma, Mingxing Li, Shulei Zhao, Man Tang
Summary: This study investigated the effects of fluoxetine on neurochemical, neurobiological, and neurobehavioral changes in different subregions of the hippocampus. The results showed that fluoxetine increased dialysate 5-HT, decreased membrane 5-HTT protein, and increased cytoplasmic fraction. Additionally, fluoxetine reduced immobility times in behavioral tests, with greater effects observed in the ventral subregion compared to the dorsal subregion.
Article
Neurosciences
Alexander V. Zholos, Mariia I. Melnyk, Dariia O. Dryn
Summary: Acetylcholine is an important neurotransmitter in visceral smooth muscles, activating M2 and M3 muscarinic receptors to cause smooth muscle excitation and contraction. This review focuses on the cellular and molecular mechanisms underlying acetylcholine-induced depolarisation and smooth muscle contraction, as well as the effects of anticholinergic drugs on gastrointestinal motility. The knowledge gained from recent studies has greatly expanded our understanding of these processes.
Article
Neurosciences
Zhenlong Li, Hsien-Yu Peng, Chau-Shoun Lee, Tzer-Bin Lin, Ming-Chun Hsieh, Cheng-Yuan Lai, Han-Fang Wu, Lih-Chyang Chen, Mei-Ci Chen, Dylan Chou
Summary: Methylone shows significant efficacy in treating depression and social deficits, making it an ideal candidate for anti-depressant medication.
Article
Neurosciences
Aline Freyssin, Allison Carles, Sarra Guehairia, Gilles Rubinstenn, Tangui Maurice
Summary: This study explores the potential of combining FENM and S1R agonists in the treatment of Alzheimer's disease. The results showed that most FENM-based combinations can protect against learning deficits caused by A beta 25-35, with better efficacy in short-term memory.
Article
Neurosciences
J. D. Lorente, J. Cuitavi, L. Rullo, S. Candeletti, P. Romualdi, L. Hipolito
Summary: This study analyzed the effects of pain on negative affect in different sexes and time courses, as well as the involvement of the dynorphinergic and corticotropin releasing factor systems in these pain-related behaviors. The results showed sex and time-dependent anxiety- and anhedonia-like behaviors induced by pain in female rats. The recruitment of KOR/DYN in the NAc was identified as a key neurological substrate mediating pain-induced behavioral alterations.
Article
Neurosciences
Rongjun Liu, Daofan Sun, Xiuzhong Xing, Qingge Chen, Bo Lu, Bo Meng, Hui Yuan, Lan Mo, Liufang Sheng, Jinwei Zheng, Qiusheng Wang, Junping Chen, Xiaowei Chen
Summary: The coexistence of pain and depression is frequently observed in patients with chronic pain and depression. Oxytocin, a neuropeptide, has been reported to relieve chronic pain and depressive symptoms. This study investigated the effect of intranasal oxytocin on neuropathic pain and comorbid depressive symptoms, and found that oxytocin attenuated depression-like behavior but did not alleviate mechanical hyperalgesia. The results suggest that intranasal oxytocin may have the potential to treat depressive symptoms in neuropathic pain patients.