Article
Pharmacology & Pharmacy
Serena Deiana, Wolfgang Hauber, Alexandra Munster, Susanne Sommer, Boris Ferger, Anelise Marti, Bernhard Schmid, Cornelia Dorner-Ciossek, Holger Rosenbrock
Summary: This study suggests that the GlyT1 inhibitor Bitopertin improves cognition and certain symptoms associated with schizophrenia, such as memory deficits, by increasing glycine levels. These findings may have important clinical implications for the treatment of diseases characterized by NMDR hypofunction, such as schizophrenia.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Imane Frouni, Dominique Bedard, Elodie Bourgeois-Cayer, Adjia Hamadjida, Fleur Gaudette, Francis Beaudry, Philippe Huot
Summary: This study determined the pharmacokinetic profile of bitopertin in female Sprague-Dawley rats, finding dose-dependent AUC and T-max that showed a linear relationship and comparable plasma levels to those achieved in the clinic. These results will be useful in designing pre-clinical experiments for the sub-cutaneous administration of this drug in the future.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Li Na Zhao, Mikael Bjorklund, Matias J. Caldez, Jie Zheng, Philipp Kaldis
Summary: Most cancer drugs have significant side effects, so understanding the biology of drug targets is crucial for developing more effective treatments. The folate-mediated one-carbon (1C) metabolism pathway has shown promise in reducing side effects. Research suggests that MTHFD2 is a good drug target in this pathway and highlights the potential of other targets as well.
Article
Pharmacology & Pharmacy
Siliang Chen, Shuxin Zhang, Wentao Feng, Junhong Li, Yunbo Yuan, Wenhao Li, Zhihao Wang, Yuan Yang, Yanhui Liu
Summary: This study investigated the expression pattern of serine and glycine metabolism-related genes (SGMGs) in glioma and found their correlation with clinicopathological features, prognosis, and immune microenvironment. By constructing a predictive model based on SGMGs, glioma patients were stratified into high and low-risk groups with different prognoses. The study also revealed the relationship between SGMGs and immune cells and validated the potential of SGMGs in guiding immunotherapy selection for glioma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Kui Wang, Li Luo, Shuyue Fu, Mao Wang, Zihao Wang, Lixia Dong, Xingyun Wu, Lunzhi Dai, Yong Peng, Guobo Shen, Hai-Ning Chen, Edouard Collins Nice, Xiawei Wei, Canhua Huang
Summary: Using integrative metabolomics and transcriptomics analyses, the study reveals that hepatocellular carcinoma (HCC) tissues have increased serine levels but decreased expression of phosphoglycerate dehydrogenase (PHGDH), a key enzyme in serine biosynthesis. The increased serine levels are obtained through enhanced PHGDH catalytic activity mediated by protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. Furthermore, PRMT1-mediated PHGDH methylation correlates with poor prognosis for HCC patients and blocking PHGDH methylation inhibits serine synthesis and restrains HCC growth.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Yuan Zhang, Kimberly J. Newsom, Mei Zhang, Jeffry S. Kelley, Petr Starostik
Summary: FLT3-ITD mutation in AML results in upregulation of de novo creatine biosynthesis through the STAT5 signaling pathway, leading to increased glycine amidinotransferase expression and higher creatinine levels. Inhibiting FLT3-ITD or targeting the creatine metabolic pathway can decrease cell proliferation and induce cell apoptosis in FLT3-ITD-mutant AML, potentially via the AMPK/mTOR signaling pathway.
MOLECULAR CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Kentaro Watanabe, Shunsuke Kimura, Masafumi Seki, Tomoya Isobe, Yasuo Kubota, Masahiro Sekiguchi, Aiko Sato-Otsubo, Mitsuteru Hiwatari, Motohiro Kato, Akira Oka, Katsuyoshi Koh, Yusuke Sato, Hiroko Tanaka, Satoru Miyano, Tomoko Kawai, Kenichiro Hata, Hiroo Ueno, Yasuhito Nannya, Hiromichi Suzuki, Kenichi Yoshida, Yoichi Fujii, Genta Nagae, Hiroyuki Aburatani, Seishi Ogawa, Junko Takita
Summary: This study analyzed DNA methylation and expression datasets of neuroblastomas to identify candidate genes associated with aggressive features. The gene PHGDH, related to serine metabolism, was found to have strong expression and characteristic methylation in a subgroup of neuroblastoma cases. Inhibition of PHGDH suppressed neuroblastoma cell proliferation both in vitro and in vivo, suggesting it as a potential therapeutic alternative. Additionally, inhibiting arginine metabolism showed a combination effect, especially on extracellular arginine-dependent neuroblastoma cells with ASS1 deficiency. The results highlight the rational therapeutic strategy of targeting serine/arginine metabolism for intractable neuroblastoma.
Article
Biology
Tian (Autumn) Qiu, Cindy J. Lee, Chen Huang, Dong-Kyu Lee, Stanislav S. Rubakhin, Elena V. Romanova, Jonathan V. Sweedler
Summary: The microbial metabolite d-alanine, derived from food and gut microbiota, accumulates in the pancreas, brain, and pituitary of mice. The sources of d-alanine in mice are shown to be microbiota and diet, rather than endogenous racemization. This research highlights the importance of investigating the biological functions of gut-microbiome derived d-alanine, especially its role in NMDAR-related activities in the microbiome-gut-brain axis.
COMMUNICATIONS BIOLOGY
(2023)
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)
Review
Clinical Neurology
Pooja Patnaik Kuppili, Vikas Menon, Gopinath Sathyanarayanan, Siddharth Sarkar, Chittaranjan Andrade
Summary: This study found that d-Cycloserine did not show significant efficacy in treating negative, cognitive, or positive symptoms of schizophrenia. Additionally, there was no significant improvement in early treatment outcomes.
JOURNAL OF NEURAL TRANSMISSION
(2021)
Article
Genetics & Heredity
Tung-Hsia Liu, Hsiao-Hui Tsou, Ren-Hua Chung, Shu Chih Liu, Sheng-Chang Wang, Hsiang-Wei Kuo, Chiu-Ping Fang, Andrew C. H. Chen, Yu-Li Liu
Summary: Methadone, a synthetic opioid used for heroin dependency, may be influenced by genetic variations in the DAO gene in terms of dosage and response.
JOURNAL OF HUMAN GENETICS
(2022)
Article
Agronomy
David B. Westerveld, Nader Soltani, David C. Hooker, Darren E. Robinson, Patrick J. Tranel, Martin Laforest, Peter H. Sikkema
Summary: The study aimed to determine the biologically effective dose of metribuzin for preemergence and postemergence application to control MS and MR waterhemp populations. Results showed that waterhemp populations with NTSR (enhanced metabolism) can be controlled by metribuzin applied preemergence and postemergence, while those with TSR (glycine-264-serine altered target site) are not controlled by metribuzin.
Review
Biochemistry & Molecular Biology
Isis Nem de Oliveira Souza, Robin Roychaudhuri, Jacqueline de Belleroche, Jean-Pierre Mothet
Summary: Free D-amino acids (D-AAs) are a novel class of signaling molecules with important roles in various organs. They have implications in neuropathologies such as schizophrenia, epilepsy, and chronic pain. Recent research has shown the essential role of D-serine, D-aspartate, and D-cysteine in the healthy development and function of the central nervous system.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Microbiology
Santiago Cuesta, Paula Burdisso, Amir Segev, Said Kourrich, Vanessa Sperandio
Summary: The study on the mechanism of the interaction between gut microbiota and cocaine found that cocaine exposure increases intestinal norepinephrine levels, which promotes intestinal colonization and leads to a series of behavioral responses. Gut microbiota affects glycine levels, and through glutamatergic transmission, influences transcriptional plasticity in the nucleus accumbens, thereby modulating reward-related brain circuits associated with SUDs.
CELL HOST & MICROBE
(2022)
Article
Behavioral Sciences
Ching-Hsun Huang, Ju-Chun Pei, Da-Zhong Luo, Ching Chen, Yi-Wen Chen, Wen-Sung Lai
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2015)
Article
Integrative & Complementary Medicine
Chao-Wei Huang, Tzu-Wen Hong, Ying-Jing Wang, Ko-Chien Chen, Ju-Chun Pei, Tai-Yuan Chuang, Wen-Sung Lai, Sheng-Hong Tsai, Richard Chu, Wei-Cheng Chen, Lee-Yan Sheen, Satoru Takahashi, Shih-Torng Ding, Tang-Long Shen
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2016)
Article
Medicine, Research & Experimental
Ming-Kai Pan, Sheng-Han Kuo, Chun-Hwei Tai, Jyun-You Liou, Ju-Chun Pei, Chia-Yuan Chang, Yi-Mei Wang, Wen-Chuan Liu, Tien-Rei Wang, Wen-Sung Lai, Chung-Chin Kuo
JOURNAL OF CLINICAL INVESTIGATION
(2016)
Article
Multidisciplinary Sciences
Chia-Yuan Chang, Yi-Wen Chen, Tsu-Wei Wang, Wen-Sung Lai
SCIENTIFIC REPORTS
(2016)
Article
Clinical Neurology
Ju-Chun Pei, Wei-Li Hung, Bei-Xuan Lin, Min-Han Shih, Liang-Yin Lu, Da-Zhong Luo, Hwan-Ching Tai, Vincent Studer, Ming-Yuan Min, Wen-Sung Lai
JOURNAL OF PSYCHOPHARMACOLOGY
(2019)
Article
Neurosciences
Jun Mukai, Enrico Cannavo, Gregg W. Crabtree, Ziyi Sun, Anastasia Diamantopoulou, Pratibha Thakur, Chia-Yuan Chang, Yifei Cai, Stavros Lomvardas, Atsushi Takata, Bin Xu, Joseph A. Gogos
Article
Multidisciplinary Sciences
Da-Zhong Luo, Chia-Yuan Chang, Tsung-Ren Huang, Vincent Studer, Tsu-Wei Wang, Wen-Sung Lai
SCIENTIFIC REPORTS
(2020)
Article
Multidisciplinary Sciences
Alan J. Park, Alexander Z. Harris, Kelly M. Martyniuk, Chia-Yuan Chang, Atheir I. Abbas, Daniel C. Lowes, Christoph Kellendonk, Joseph A. Gogos, Joshua A. Gordon
Summary: Novelty helps reset neural circuits in the brain to promote adaptive learning. Exposure to novelty environment reorganizes neural circuits in mice, enhancing learning-related plasticity, and this effect can be mediated by dopamine D1 receptors.
Review
Biochemistry & Molecular Biology
Chia-Yuan Chang, Da-Zhong Luo, Ju-Chun Pei, Ming-Che Kuo, Yi-Chen Hsieh, Wen-Sung Lai
Summary: Cognitive dysfunction is a core symptom in schizophrenia and has predictive value for functional outcomes, with current research focusing on potential contributions of glial cells outside of neurons. While the exact role of astrocytes in schizophrenia remains uncertain, accumulated evidence suggests they may play a significant role in the pathogenesis of the disorder.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Biomedical
Zu-Jia Lo, Yuan-Chuan Wang, Yun-Jie Huang, Ren-Yong Hung, Yi-Heng Wu, Tzu-Yun Wang, Yang-Jing Huang, Hui-Chun Huang, Yu-Cheng Lu, Sheng-Yu Peng, Chia-Yuan Chang, Wen-Sung Lai, Yu-Juei Hsu
Summary: The proposed ACABA is a reconfigurable differential-to-single-ended buffer amplifier based on floating-gate technologies, capable of adjusting output level and bandwidth autonomously, with variable gain. It increases current consumption spontaneously when processing fast or large signals, achieving a high slew rate, but decreases back to low quiescent level when the output voltage reaches equilibrium.
IEEE TRANSACTIONS ON BIOMEDICAL CIRCUITS AND SYSTEMS
(2021)
Article
Biochemistry & Molecular Biology
Greer S. Kirshenbaum, Chia-Yuan Chang, Maria Bompolaki, Victoria R. Bradford, Joseph Bell, Stylianos Kosmidis, Rebecca M. Shansky, Javier Orlandi, Lisa M. Savage, Alexander Z. Harris, E. David Leonardo, Alex Dranovsky
Summary: Adult neurogenesis is reduced during aging and impaired in stress, memory, and cognition disorders, but its normal function is still unclear. This study found that long-term suppression of neurogenesis led to a decline in hippocampal acetylcholine signaling and working memory deficits. However, compensatory reorganization of the cholinergic dentate gyrus inputs and recruitment of different neuronal projections helped correct the memory dysfunction. These findings highlight the importance of hippocampal neurogenesis in memory maintenance and provide insights into the progressive nature of memory deterioration.
MOLECULAR PSYCHIATRY
(2023)