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Discovery of Selenium-Containing Derivatives as Potent and Orally Bioavailable GLP-1R Agonists.
J Med Chem
January 2025
Jiang Su Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Glucagon-like peptide-1 receptor (GLP-1R) is a well-established target for the treatment of type 2 diabetes mellitus (T2DM) and obesity. The development of orally bioavailable and long-acting small-molecule GLP-1R agonists is a pursuit in both academia and industry. Herein, new selenium (Se)-containing compounds were designed using a Se-oxygen bioisostere strategy on the danuglipron scaffold.
View Article and Find Full Text PDFPhosphodiesterase 4D inhibition improves the functional and molecular outcome in a mouse and human model of Charcot Marie Tooth disease 1 A.
Biomed Pharmacother
January 2025
Laboratory for Functional Imaging & Research on Stem Cells, BIOMED, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium. Electronic address:
Charcot-Marie-Tooth disease type 1A (CMT1A) is an inherited peripheral neuropathy caused by a duplication of the peripheral myelin protein 22 (PMP22) gene. It is primarily marked by Schwann cell dedifferentiation and demyelination, leading to motor and sensory deficits. Cyclic adenosine monophosphate (cAMP) is crucial for Schwann cell differentiation and maturation.
View Article and Find Full Text PDFAction potential-independent spontaneous microdomain Ca transients-mediated continuous neurotransmission regulates hyperalgesia.
Proc Natl Acad Sci U S A
January 2025
Department of Neurology, the Second Affiliated Hospital, Neuroscience Research Center, Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710000, China.
Neurotransmitters and neuromodulators can be released via either action potential (AP)-evoked transient or AP-independent continuous neurotransmission. The elevated AP-evoked neurotransmission in the primary sensory neurons plays crucial roles in hyperalgesia. However, whether and how the AP-independent continuous neurotransmission contributes to hyperalgesia remains largely unknown.
View Article and Find Full Text PDF1-Methylxanthine enhances memory and neurotransmitter levels.
PLoS One
January 2025
Radiant Research Services Pvt. Ltd., Bangalore, India.
1-Methylxanthine (1-MX) is the major metabolite of caffeine and paraxanthine and might contribute to their activity. 1-MX is an adenosine receptor antagonist and increases the release and survivability of neurotransmitters; however, no study has addressed the potential physiological effects of 1-MX ingestion. The aim of this study was to compare the effect of 1-MX on memory and related biomarkers in rats compared to control.
View Article and Find Full Text PDFIn the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia.
Clin Psychopharmacol Neurosci
February 2025
Department of Mental Health of Enna, Psychiatry Unity, Enna Hospital, Enna, Italy.
Intracellular cyclic nucleotides (cyclic adenosine monophosphate and cyclic guanosine monophosphate) and downstream cellular signal transduction are regulated by phosphodiesterases (PDEs). The neuroplasticity, neurotransmitter pathways, and neuroinflammation-controlling functions of PDEs were demonstrated in numerous in vitro and animal model studies. We comprehensively reviewed the literature regarding the expression of PDEs in various brain regions.
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