Article
Biochemistry & Molecular Biology
Martyna Z. Wrobel, Andrzej Chodkowski, Maciej Dawidowski, Agata Siwek, Katarzyna Stachowicz, Bernadeta Szewczyk, Gabriel Nowak, Grzegorz Satala, Andrzej J. Bojarski, Jadwiga Turlo
Summary: The synthesis and evaluation of new compounds targeting the serotonin 1A receptors and serotonin transporter in the treatment of central nervous system diseases, especially depression, were conducted. Compound 4f emerged as the most promising with good activity, stability, and potential as a therapeutic agent.
BIOORGANIC CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
William H. Powell, Lucy E. Annett, Ronan Depoortere, Adrian Newman-Tancredi, Mahmoud M. Iravani
Summary: Anxiety is a common neuropsychiatric disorder with abnormalities in serotonergic function playing a role in its pathogenesis. NLX-112, a highly selective 5-HT1A receptor full agonist, has been shown to alleviate anxiety-like behaviors in mice, potentially possessing anxiolytic properties.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Barbara A. Bricker, Chandrashekhar Voshavar, Edem K. Onyameh, Uma M. Gonela, Xinsong Lin, Tracy L. Swanson, Laura B. Kozell, Jennifer L. Schmachtenberg, Shelley H. Bloom, Aaron J. Janowsky, Seth Y. Ablordeppey
Summary: In this study, we synthesized and separated the enantiomers of SYA0340, identified their absolute configurations, and evaluated their binding affinities and functional characteristics at the 5-HT1A and 5-HT7A receptors. The results showed that both enantiomers have similar agonist properties at the 5-HT1A receptor and antagonist properties at the 5-HT7A receptor, with SYA0340-P1 displaying higher potency as a 5-HT1A receptor antagonist. Therefore, SYA0340-P1 is considered the eutomer and these enantiomers may serve as new pharmacological probes for the 5-HT1A and 5-HT7A receptors.
Article
Neurosciences
Marcus Saarinen, Ioannis Mantas, Ivana Flais, Richard Agren, Kristoffer Sahlholm, Mark J. Millan, Per Svenningsson
Summary: SEP-383856 (SEP-856) is a novel antipsychotic with a unique pattern of receptor interaction, showing agonist activity at TAAR1 and 5-HT1A receptors. Research indicates its potential advantages in treating schizophrenia and other psychotic disorders.
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Rui-Xiang Yuan, Ke-Yu Jiang, Jian-Wei Wu, Zi-Xue Zhang, Mi-Si Li, Jian-Qi Li, Feng Ni
Summary: A series of novel compounds were synthesized and evaluated for their antidepressant properties. Compound 12a showed superior serotonin reuptake inhibition and good metabolic stability, indicating its potential as a new antidepressant candidate.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Clinical Neurology
Rafael Pazinatto de Aguiar, Adrian Newman-Tancredi, Jos Prickaerts, Rubia Maria Weffort de Oliveira
Summary: This review focuses on the roles and mechanisms of 5-HT1A receptors in neuroprotection in experimental models of cerebral ischemia, with experimental evidence suggesting that 5-HT1A receptor agonists can prevent neuronal damage and promote functional recovery induced by ischemia.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Gastroenterology & Hepatology
Jens Walldorf, Marc Porzner, Martin Neumann, Golsa Joodi, Jan Hendrik Niess, Georg von Boyen, Karsten Maeder, Julia Weissbach, Alexander Kleger, Thomas Seufferlein
Summary: The selective 5-HT1A receptor agonist SR57746A shows potential as a neuroprotective agent in the gastrointestinal tract, preventing apoptosis of intestinal epithelial cells and enteric glial cells, and reducing mucosal injury in inflammatory bowel disease models.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Neurosciences
Ronan Yves Depoortere, Agnes Laure Auclair, Adrian Newman-Tancredi
Summary: NLX-101, a biased agonist at post-synaptic cortical 5-HT1A receptors, was found to protect against scopolamine-induced cognitive impairment, reversing deficits at 5 and 10 s delays. Compared to the acetylcholinesterase inhibitor tacrine, NLX-101 exhibited stronger and more dose-dependent effects.
Review
Biochemistry & Molecular Biology
Irina P. Voronova
Summary: This review discusses the influence of serotonin receptors on body temperature regulation in warm-blooded animals, covering different receptor types and their activation effects on temperature.
Article
Neurosciences
Benjamin Vidal, Elise Levigoureux, Sarah Chaib, Caroline Bouillot, Thierry Billard, Adrian Newman-Tancredi, Luc Zimmer
Summary: The study revealed that the binding sites of 5-HT1A receptor agonists and antagonists are differently modified in Parkinson's disease and levodopa-induced dyskinesia. The functional state of 5-HT1A receptors plays a significant role in levodopa-induced dyskinesia, emphasizing the importance of characterizing this state using agonist radiotracers in both physiological and pathological conditions.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
D'bora Dreher Nabinger, Stefani Altenhofen, Alexis Buatois, Amanda Facciol, Julia Vasconcellos Peixoto, Julia Maria Kuhl da Silva, Diptendu Chatterjee, Gabriel Rubensam, Robert Gerlai, Carla Denise Bonan
Summary: This study investigated the effects of the dopamine D2/D3 receptor agonist quinpirole on the behavior, brain-derived neurotrophic factor (BDNF), and neurotransmitter levels in adult zebrafish. The results showed that quinpirole administration caused decreased locomotor activity, increased anxiety-like behaviors, memory impairment, and stereotypic swimming in zebrafish. Furthermore, quinpirole treatment also decreased the number of BDNF-immunoreactive cells and altered glutamate and serotonin levels in the zebrafish brain. These findings suggest that quinpirole administration in adult zebrafish can be a useful tool for studying the mechanisms underlying neurological disorders related to the dopaminergic system.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Pharmacology & Pharmacy
Hirohito Esaki, Yuki Sasaki, Naoya Nishitani, Hikari Kamada, Satoko Mukai, Yoshitaka Ohshima, Sao Nakada, Xiyan Ni, Satoshi Deyama, Katsuyuki Kaneda
Summary: This study examined whether the prosocial effects induced by MDMA are mediated by 5-HT neurotransmission in the medial prefrontal cortex (mPFC) and the basolateral nucleus of amygdala (BLA). The results showed that selective inhibition of 5-HT transporters before MDMA administration did not suppress the prosocial effects. However, the 5-HT1A receptor antagonist WAY100635 significantly suppressed the prosocial effects of MDMA. Furthermore, local administration of WAY100635 into the BLA, but not the mPFC, suppressed the MDMA-induced prosocial effects. These findings suggest that MDMA induces prosocial effects through the stimulation of 5-HT1A receptors in the BLA.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Behavioral Sciences
A. Ezequiel Pereyra, Camilo J. Mininni, B. Silvano Zanutto
Summary: The study demonstrates that serotonin modulates reward-driven learning, and 5-HT1A receptors in the BLA play a crucial role in extinction. Fluoxetine treatment accelerates extinction learning, while BLA lesions partially revert this effect.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Matthieu Colom, Benjamin Vidal, Sylvain Fieux, Jerome Redoute, Nicolas Costes, Franck Lavenne, Ines Merida, Zacharie Irace, Thibaud Iecker, Caroline Bouillot, Thierry Billard, Adrian Newman-Tancredi, Luc Zimmer
Summary: The study evaluated the sensitivity of the radiopharmaceutical [F-18]F13640 to endogenous serotonin release, demonstrating its effectiveness in measuring neurotransmitter fluctuations but highlighting the importance of longer PET scans for accurate displacement measurements.
FRONTIERS IN NEUROSCIENCE
(2021)
Review
Clinical Neurology
Eric D. D. Achtyes, Seth C. C. Hopkins, Nina Dedic, Heather Dworak, Courtney Zeni, Kenneth Koblan
Summary: Ulotaront is a TAAR1 agonist being developed for the treatment of schizophrenia. It was discovered through a target-agnostic approach and has shown antipsychotic-like effects in vivo. The mechanism of action is believed to involve activation of TAAR1 and 5-HT1A receptors. Ulotaront has shown potential as a first-in-class treatment for schizophrenia with a distinct safety and efficacy profile compared to current antipsychotics.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Shuang-Qi Gao, Hai Zhang, Jin-Gang He, Hui-Ling Zheng, Pei-Wei Zhang, Jun-Feng Xu, Zu-Cheng Shen, Huan-Huan Zhao, Fang Wang, Zhuang-Li Hu, Jian-Guo Chen
Review
Pharmacology & Pharmacy
John L. Waddington, Xuechu Zhen, Colm M. P. O'Tuathaigh
FRONTIERS IN PHARMACOLOGY
(2020)
Editorial Material
Chemistry, Multidisciplinary
Xue-chu Zhen, Hong-Yuan Chu
ACTA PHARMACOLOGICA SINICA
(2020)
Article
Immunology
Chaojun Han, Pengju Yan, Tao He, Junjie Cheng, Wenhua Zheng, Long-Tai Zheng, Xuechu Zhen
BRAIN BEHAVIOR AND IMMUNITY
(2020)
Article
Cell Biology
Wu Jing, Yang Huicui, Cheng Junjie, Zhang Li, Ke Youliang, Zhu Yi, Wang Cheng, Zhang Xiaohu, Zhen Xuechu, Zheng Long Tai
JOURNAL OF CELLULAR PHYSIOLOGY
(2020)
Article
Cell Biology
Xia Zhao, Linlin Liu, Yizhou Jiang, Marta Silva, Xuechu Zhen, Wenhua Zheng
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2020)
Article
Biochemistry & Molecular Biology
Steven F. Grieco, Xin Qiao, Xiaoting Zheng, Yongjun Liu, Lujia Chen, Hai Zhang, Zhaoxia Yu, Jeffrey P. Gavornik, Cary Lai, Sunil P. Gandhi, Todd C. Holmes, Xiangmin Xu
Review
Neurosciences
Ming-ming Xu, Mao-tian Zhou, Shu-wei Li, Xue-chu Zhen, Shuang Yang
Summary: Neurodegenerative diseases such as Alzheimer's and Parkinson's are incurable and progressively debilitating conditions that mainly affect the elderly. Research has found that protein glycosylation plays a crucial role in these diseases, with abnormal changes indicating altered biological pathways in disease progression. Early detection of neurodegenerative diseases is being explored through the use of specific glycosylation changes in cerebrospinal fluid, blood, and urine as potential biomarkers.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Yu Zhang, Lei Xu, Yao Zhang, Jie Pan, Pu-qing Wang, Sheng Tian, Huan-ting Li, Bo-wen Gao, Ting-jun Hou, Xue-chu Zhen, Long-Tai Zheng
Summary: This study identified 12 compounds with better bioactivity than ISO-1 as MIF inhibitors, with compound 11 showing marked anti-inflammatory efficacy in LPS-activated BV-2 microglial cells by suppressing NF-κB and MAPKs activation. These findings suggest that small-molecule MIF inhibitors could be promising therapeutic agents for neuroinflammatory diseases.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Immunology
Long-Tai Zheng, Jiaojiao Chen, Li Zhang, Yu Zhang, Lei Xu, Tingjun Hou, Xuechu Zhen, Qijun Dai, Hua Liu
Summary: This study demonstrated that the MIF inhibitor Z-312 possesses significant anti-inflammatory effects in LPS-induced neuroinflammation by reducing proinflammatory cytokine production and modulating NF-κB and MAPK signaling pathways. Furthermore, in a PD mouse model, Z-312 markedly ameliorated microglial activation and subsequent DA neuron loss. The findings suggest that Z-312 may be a promising neuroprotective agent for the treatment of neuroinflammation-mediated neurological diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Junjie Cheng, Rong Zhang, Zhirou Xu, Youliang Ke, Renjuan Sun, Huicui Yang, Xiaohu Zhang, Xuechu Zhen, Long-Tai Zheng
Summary: The study suggests that glycolysis plays a crucial role in microglial activation and inhibiting glycolysis can attenuate neuroinflammatory diseases associated with microglial activation.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Mingmei Wang, Chunlei Wan, Tao He, Chaojun Han, Kailian Zhu, John L. Waddington, Xuechu Zhen
Summary: Mitochondria play a crucial role in Parkinson's disease, and mitophagy is essential for the survival of DA neurons. The sigma-1 receptor modulates mitophagy, providing protection for DA neurons in a PD-like mouse model.
Article
Chemistry, Multidisciplinary
Peng-ju Yan, Zhao-xiang Ren, Zhi-feng Shi, Chun-lei Wan, Chao-jun Han, Liu-shuai Zhu, Ning-ning Li, John L. Waddington, Xue-chu Zhen
Summary: This study reveals that deficiency of Clk1 suppresses METH-induced conditioned place preference (CPP) and increases DAT expression on the cell membrane of striatum and hippocampus. The decrease in iron content in the brain regions is due to elevated expression of iron exporter ferroportin 1 (FPN1) associated with increased expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in response to Clk1 deficiency. Iron plays a critical role in mediating Clk1 deficiency-induced alterations in DAT expression via upstream HIF-1 alpha.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Neurosciences
Tao He, Chaojun Han, Chun Liu, Jiaojiao Chen, Huicui Yang, Longtai Zheng, John L. Waddington, Xuechu Zhen
Summary: This study found that methamphetamine abuse can lead to damage of dopaminergic neurons, and revealed the important role of D1 receptors in this damage. The study also found that the AMPK/FOXO3A pathway mediates the activation of autophagy mediated by D1 receptors.
PSYCHOPHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Zheng Ying, Na Ye, Qilian Ma, Fan Chen, Ningning Li, Xuechu Zhen
Summary: Significant evidences show that sub-cellular organelle dynamics play a critical role in physiological and pathological events, making them attractive drug targets. However, drug development in this field is still limited despite extensive studies on the biological mechanisms. This review explores the potential of targeting organelle dynamics in the central nervous system, specifically mitochondrial dynamics and ER-organelle membrane contact dynamics, for treating neurodegenerative diseases.
ADVANCED DRUG DELIVERY REVIEWS
(2023)
