Gambierol: Synthetic Aspects

Fuwa, Haruhiko

doi:10.1201/b16662-31

Cited by 14 publications

(1 citation statement)

References 39 publications

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“…Marine polycyclic ethers have fascinated the scientific community for their complex molecular structures and their potent and wide range of biological activities . Gambierol has evoked an important neurotoxicity in mammalian cells as well as an acute lethal toxicity in mice (50 μg/kg, ip) .…”

Section: Resultsmentioning

confidence: 99%

Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology

Albrecht

Vieira

Rodríguez

et al. 2017

ACS Chem. Neurosci.

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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 β 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-methyl-d-aspartate (NMDA) receptor. The combined effect of this compound on amyloid β and tau phosphorylation represents a multitarget therapeutic approach for AD which might be more effective for this multifactorial and complex neurodegenerative disease than the current treatments.

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Section: Resultsmentioning

confidence: 99%

Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology

Albrecht

Vieira

Rodríguez

et al. 2017

ACS Chem. Neurosci.

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Determination of Saxitoxin, Tetrodotoxin and Common Phycotoxins

Botana

Alfonso

Vieytes

et al. 2017

Analysis of Food Toxins and Toxicants

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Azaspiracid Toxins: Toxicological Profile

Heß

Twiner

Kilcoyne³

et al. 2016

Marine and Freshwater Toxins

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Azaspiracids (AZAs) are a toxin group that originate from marine dinoflagellates of the genera Azadinium and Amphidoma. After accumulation of these toxins in edible marine organisms and their subsequent consumption, humans develop a gastrointestinal syndrome referred to as azaspiracid shellfish poisoning (AZP). This syndrome is very similar to diarrheic shellfish poisoning (DSP), with main symptoms appearing after a few hours from consumption and including diarrhea, vomiting, and stomach cramps. Due to extensive metabolism in shellfish, more than 30 analogues have been reported to date, and purified compounds for selected analogues have recently been made available for toxicological studies. Currently, only AZA1, AZA2, and AZA3 are regulated in Europe and internationally; however, more recent evidence suggests that AZA6, AZA17, and AZA19 may also be analogues of importance for estimating the full risk of seafood. Even though animal studies have pointed out target organs (digestive tract, liver, heart, and lung), mechanism of action studies at cellular level are not yet conclusive. While a number of common targets have been excluded (protein phosphatases, kinases, actin depolymerization, G proteincoupled receptors), some evidence points toward ion channel activity of AZAs. Still, in vitro studies do not correlate well with symptoms observed in humans. Also, while some animal studies point toward longer-term effects, no such evidence has been reported from human poisoning events. However, it should be noted that in-depth epidemiological studies are still lacking. Even though all risk assessments have based their evaluation on a single, relatively early poisoning event in 1997, in Arranmore Island, Ireland, producing organisms and toxin occurrences have been reported worldwide, and further occurrence studies should provide a better base for such epidemiological studies.

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Gambierol: Synthetic Aspects

Cited by 14 publications

References 39 publications

Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology

Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology

Determination of Saxitoxin, Tetrodotoxin and Common Phycotoxins

Azaspiracid Toxins: Toxicological Profile

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