Abstract
Spirolides are marine toxins that are not currently in the routine monitoring assays. Nicotinic receptors seem to be the target of these compounds making them a promising pharmacological tool for related diseases as dementias as previously shown in vitro. In the present work, the bioavailability of 13-desMethyl spirolide C (13-desMeC) in the brain and in vivo effects were tested. Bioavailability was studied by ultra-performance liquid chromatography-mass spectrometry and its effect over Alzheimer hallmarks was studied by Proton magnetic resonance spectroscopy (H-MRS) and western blot. Only 2 minutes after its intraperitoneal injection it is found in brain and remains detectable even 24 hours post administration. Based on previous works that showed beneficial effects in an in vitro model of Alzheimer´s disease (AD), we studied the effect in the same mice, 3xTg-AD, in vivo. We found that 13-desMeC (11.9 ug/kg, i.p.) induced positive effects on AD markers with an increase in N-acetyl aspartate (NAA) levels. These results were supported by an increase in synaptophysin levels and also a decrease in the intracellular amyloid beta levels in the hippocampus of treated 3xTg- AD versus non treated mice remarking the positive effects of this molecule in a well known model of AD.
These data indicate for the first time that 13-desMeC cross the blood brain barrier and shows in vivo beneficial effects against AD after administration of low intraperitoneal doses of this marine toxin. This toxin may inspire a novel medical treatment of age-related diseases.
Keywords: Spirolide, marine toxin, Alzheimer, resonance magnetic, tau, beta-amyloid
Current Alzheimer Research
Title:Benefit of 13-desmethyl Spirolide C Treatment in Triple Transgenic Mouse Model of Alzheimer Disease: Beta-Amyloid and Neuronal Markers Improvement
Volume: 10 Issue: 3
Author(s): Eva Alonso, Paz Otero, Carmen Vale, Amparo Alfonso, Alvaro Antelo, Lydia Gimenez-Llort, Laurent Chabaud, Catherine Guillou and Luis M. Botana
Affiliation:
Keywords: Spirolide, marine toxin, Alzheimer, resonance magnetic, tau, beta-amyloid
Abstract: Spirolides are marine toxins that are not currently in the routine monitoring assays. Nicotinic receptors seem to be the target of these compounds making them a promising pharmacological tool for related diseases as dementias as previously shown in vitro. In the present work, the bioavailability of 13-desMethyl spirolide C (13-desMeC) in the brain and in vivo effects were tested. Bioavailability was studied by ultra-performance liquid chromatography-mass spectrometry and its effect over Alzheimer hallmarks was studied by Proton magnetic resonance spectroscopy (H-MRS) and western blot. Only 2 minutes after its intraperitoneal injection it is found in brain and remains detectable even 24 hours post administration. Based on previous works that showed beneficial effects in an in vitro model of Alzheimer´s disease (AD), we studied the effect in the same mice, 3xTg-AD, in vivo. We found that 13-desMeC (11.9 ug/kg, i.p.) induced positive effects on AD markers with an increase in N-acetyl aspartate (NAA) levels. These results were supported by an increase in synaptophysin levels and also a decrease in the intracellular amyloid beta levels in the hippocampus of treated 3xTg- AD versus non treated mice remarking the positive effects of this molecule in a well known model of AD.
These data indicate for the first time that 13-desMeC cross the blood brain barrier and shows in vivo beneficial effects against AD after administration of low intraperitoneal doses of this marine toxin. This toxin may inspire a novel medical treatment of age-related diseases.
Export Options
About this article
Cite this article as:
Alonso Eva, Otero Paz, Vale Carmen, Alfonso Amparo, Antelo Alvaro, Gimenez-Llort Lydia, Chabaud Laurent, Guillou Catherine and M. Botana Luis, Benefit of 13-desmethyl Spirolide C Treatment in Triple Transgenic Mouse Model of Alzheimer Disease: Beta-Amyloid and Neuronal Markers Improvement, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030007
DOI https://dx.doi.org/10.2174/1567205011310030007 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Wnt / β-Catenin Signaling Pathway as Novel Cancer Drug Targets
Current Cancer Drug Targets An Orally Bioavailable c-Met Kinase Inhibitor Potently Inhibits Brain Tumor Malignancy and Growth
Anti-Cancer Agents in Medicinal Chemistry Editorial (Thematic Issue: Novel Pharmaceutical Approaches by Natural Compound-Derived Epigenetic Regulators: Epigenetic Readers, Writers and Erasers as Therapeutic Targets)
Current Topics in Medicinal Chemistry Rhenium-188 and Copper-67 Radiopharmaceuticals for the Treatment of Bladder Cancer
Mini-Reviews in Medicinal Chemistry Molecularly Guided Therapy of Neuroblastoma: A Review of Different Approaches
Current Pharmaceutical Design Cordycepin Suppresses Integrin/FAK Signaling and Epithelial-Mesenchymal Transition in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry BACE Inhibitors as Potential Therapeutics for Alzheimers disease
Recent Patents on CNS Drug Discovery (Discontinued) Activities of Venom Proteins and Peptides with Possible Therapeutic Applications from Bees and WASPS
Protein & Peptide Letters Ag+ Complexes as Potential Therapeutic Agents in Medicine and Pharmacy
Current Medicinal Chemistry RANKL/RANK/OPG: Key Therapeutic Target in Bone Oncology
Current Drug Discovery Technologies Glioma Stem Cell Maintenance: The Role of the Microenvironment
Current Pharmaceutical Design Regulating TRAIL Receptor-Induced Cell Death at the Membrane: A Deadly Discussion
Recent Patents on Anti-Cancer Drug Discovery Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets Recent Inventions on Receptor Tyrosine Kinase RET Modulation
Recent Patents on Biotechnology Apoptosis and Autophagy Induction As Mechanism of Cancer Prevention by Naturally Occurring Dietary Agents
Current Drug Targets A Filter Based Feature Selection Algorithm Using Null Space of Covariance Matrix for DNA Microarray Gene Expression Data
Current Bioinformatics Molecular Targeted Magnetic Resonance Imaging of Human Colorectal Carcinoma (LoVo) Cells Using Novel Superparamagnetic Iron Oxide- Loaded Nanovesicles: In Vitro and in vivo Studies
Current Cancer Drug Targets The Therapeutical Potential of a Novel Pterocarpanquinone LQB-118 to Target Inhibitor of Apoptosis Proteins in Acute Myeloid Leukemia Cells
Anti-Cancer Agents in Medicinal Chemistry The Potential of Microalgae for the Production of Bioactive Molecules of Pharmaceutical Interest
Current Pharmaceutical Biotechnology Familial Alzheimers Disease Mutations in Presenilin 1 Do Not Alter Levels of the Secreted Amyloid-β Protein Precursor Generated by β-Secretase Cleavage
Current Alzheimer Research