Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent
| Autor: | Lyndon M. West, Stacee Lee Caplan, Ken Dawson-Scully, Catherine A. White, Bo Zheng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine neuromodulatory agent Pseudopterosin A Pharmaceutical Science Neurotransmission Bioinformatics medicine.disease_cause Synaptic Transmission Article octocoral Synapse Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery medicine Animals oxidative stress Tissue Distribution Glycosides pseudopterosins lcsh:QH301-705.5 Pharmacology Toxicology and Pharmaceutics (miscellaneous) Neurotransmitter Agents biology Drug discovery Mechanism (biology) Brain blood-brain barrier biology.organism_classification Pseudopterogorgia elisabethae Drosophila melanogaster 030104 developmental biology lcsh:Biology (General) chemistry Injections Intravenous Synapses Diterpenes Neuroscience 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | Marine Drugs; Volume 14; Issue 3; Pages: 55 Marine Drugs, Vol 14, Iss 3, p 55 (2016) Marine Drugs |
| ISSN: | 1660-3397 |
| DOI: | 10.3390/md14030055 |
| Popis: | Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent. |
| Databáze: | OpenAIRE |
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