Acetylcholineestarase-Inhibiting Alkaloids from Lycoris radiata Delay Paralysis of Amyloid Beta-Expressing Transgenic C. elegans CL4176
Open Access
- 13 May 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (5), e63874
- https://doi.org/10.1371/journal.pone.0063874
Abstract
The limited symptom relief and side effects of current Alzheimer’s disease (AD) medications warrant urgent discovery and study of new anti-AD agents. The “cholinergic hypothesis” of AD prompts us to search for plant-derived acetylcholineesterase (AChE) inhibitors such as galanthamine that has been licensed in Europe for AD treatment. We used the unique amyloid β-expressing transgenic C. elegans CL4176, which exhibits paralysis when human Aβ1–42 is induced, to study two natural benzylphenethylamine alkaloids isolated from Lycoris radiata (L’ Her.) Herb, galanthamine and haemanthidine, and their synthetic derivatives 1,2-Di-O-acetyllycorine and 1-O-acetyllycorine for their anti-paralysis effects. Our data indicate that these Lycoris compounds effectively delay the paralysis of CL4176 worms upon temperature up-shift, and prolong the lives of these transgenic worms. Lycoris compounds were shown to significantly inhibit the gene expression of ace-1 and ace-2. Additionally, the Lycoris compounds may modulate inflammatory and stress-related gene expressions to combat the Aβ-toxicity in C. elegans.Keywords
This publication has 34 references indexed in Scilit:
- Decreased Clearance of CNS β-Amyloid in Alzheimer’s DiseaseScience, 2010
- Assaying β-amyloid Toxicity using a Transgenic C. elegans ModelJournal of Visualized Experiments, 2010
- Biological Evaluation of Structurally Diverse Amaryllidaceae Alkaloids and their Synthetic Derivatives: Discovery of Novel Leads for Anticancer Drug DesignPlanta Medica, 2009
- A Century of Alzheimer's DiseaseScience, 2006
- C. elegans models of age-associated neurodegenerative diseases: Lessons from transgenic worm models of Alzheimer’s diseaseExperimental Gerontology, 2006
- Nematode acetylcholinesterases are encoded by multiple genes and perform non-overlapping functionsChemico-Biological Interactions, 2005
- Acetylcholinesterase inhibitors effects on oncostatin-M, interleukin-1β and interleukin-6 release from lymphocytes of Alzheimer's disease patientsExperimental Gerontology, 2005
- Acetylcholinesterase Enzyme Inhibitory Effects of Amaryllidaceae AlkaloidsPlanta Medica, 2004
- Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammationNature, 2002
- Structure and promoter activity of the 5′ flanking region of ace-1, the gene encoding acetylcholinesterase of class A in Caenorhabditis elegansJournal of Molecular Biology, 1999