Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology
| Autor: | Luis M. Botana, Yuto Suga, Rebeca Alvariño, Eva Alonso, Andrés C. Vieira, Haruhiko Fuwa, Makoto Sasaki, Inés Rodríguez, Amparo Alfonso, José Manuel Cifuentes, Sandra Gegunde |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Amyloid Physiology Cognitive Neuroscience medicine.medical_treatment Intraperitoneal injection Mice Transgenic tau Proteins Pharmacology Biochemistry Receptors N-Methyl-D-Aspartate Ciguatoxins 03 medical and health sciences Mice 0302 clinical medicine In vivo Alzheimer Disease medicine Animals Phosphorylation Glycogen synthase Amyloid beta-Peptides biology Chemistry Brain Cell Biology General Medicine In vitro 030104 developmental biology biology.protein NMDA receptor Marine toxin 030217 neurology & neurosurgery |
| Zdroj: | ACS chemical neuroscience. 8(6) |
| ISSN: | 1948-7193 |
| Popis: | Gambierol and its two, tetra- and heptacyclic, analogues have been previously proved as promising molecules for the modulation of Alzheimer’s disease (AD) hallmarks in primary cortical neurons of 3xTg-AD fetuses. In this work, the effect of the tetracyclic analogue of gambierol was tested in vivo in 3xTg-AD mice (10 months old) after 1 month of weekly treatment with 50 μg/kg. Adverse effects were not reported throughout the whole treatment period and no pathological signs were observed for the analyzed organs. The compound was found in brain samples after intraperitoneal injection. The tetracyclic analogue of gambierol elicited a decrease of amyloid β1–42 levels and a dose-dependent inhibition of β-secretase enzyme-1 activity. Moreover, this compound also reduced the phosphorylation of tau at the 181 and 159/163 residues with an increase of the inactive isoform of the glycogen synthase kinase-3β. In accordance with our in vitro neuronal model, this compound produced a reduction in the N2A subunit of the N... |
| Databáze: | OpenAIRE |
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