Tag Archives: toxins

Pharmacological potential discovered in toxins found in crustacean venom from Mayan underwater caves

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Xibalbanus turmensisThe poisonous remipede, found in the caves of Antiarin on the Yucatan Peninsula, is the only crustacean for which a venom system has been described.

Xibalbanus turmensis. Image credit: Pinheiro-Junior others., doi: 10.1186/s12915-024-01955-5.

“Poisonous animals inject toxic compounds into other organisms primarily for self-defense or predation,” said Dr. Björn von Roymont, a researcher at Goethe University Frankfurt, and his colleagues.

“Many venoms are composed of proteins that have evolved to modulate various physiological functions in the target organism.”

“Studying these biological activities could lead to pharmacological or agrochemical applications.”

“The majority of thoroughly studied venoms and venomous proteins originate from iconic terrestrial groups, primarily snakes, spiders, scorpions, and insects,” the researchers said.

“Research attention to marine life has been limited, with only a few fish and invertebrates being better studied, such as sea anemones, jellyfish, cone snails, cephalopods, polychaetes, and more recently nemertes.”

“Venoms and their toxic proteins have evolved independently in different animal lineages, so the study of new lineages provides an opportunity to identify novel toxic compounds with interesting biological activities, on the one hand, and generally convergent proteins on the other hand. It provides an opportunity to improve our understanding of the evolution of functional traits.”

In their study, the researchers investigated the biological activity of peptides found in crustacean venom. Xibalbanus turmensis.

This underwater cave-dwelling crustacean belongs to the following classes: Remipediafirst described in the 1980s and currently consists of 28 extant species.

“Xibalbanus turmensis They live in cenotes, underwater caves in Mexico's Yucatan Peninsula,” the scientists said.

“Cave dwellers directly inject the venom produced by their venom glands into their prey.”

“This toxin contains a variety of components, including a new type of peptide named cibalbin after the crustacean producer.”

“Some of these sibalbins contain characteristic structural elements that are well known to other toxins, especially those produced by spiders. Some amino acids (cysteine) in the peptide are tied together like a knot. are connected to each other in such a way that they form a structure.

“This makes the peptide more resistant to enzymes, heat, and extreme pH values.”

“Such knots often act as neurotoxins, interacting with ion channels to paralyze prey. This effect has also been proposed for some cibalbins.”

This study shows that all sibalbin peptides tested by the team, particularly Xib1, Xib2, and Xib13, effectively inhibit potassium channels in mammalian systems.

“This inhibition is very important when developing drugs to treat a variety of neurological diseases, including epilepsy,” Dr. von Roymont said.

“Xib1 and Xib13 also exhibit the ability to inhibit voltage-gated sodium channels, such as those found in neurons and cardiomyocytes.”

“Furthermore, in higher mammalian sensory neurons, the two peptides can activate two proteins involved in signal transduction: the kinases PKA-II and ERK1/2.”

“The latter suggests that they are involved in pain sensitization, opening the door to new approaches in pain treatment.”

of the team findings Published in a magazine BMC biology.

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EL Pinheiro – Junior others. 2024. Xibalbin mutants divergently evolved from remipede toxin inhibit potassium channels and activate PKA-II and Erk1/2 signaling. BMC biol 22, 164; doi: 10.1186/s12915-024-01955-5

Source: www.sci.news

Slowing Alzheimer’s Disease Progression: How Light and Sound Can Remove Toxins from the Brain

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Cross-section of a mouse brain highlighting neurons that appear to release molecules that increase toxin clearance

Tsai Laboratory/MIT Picower Laboratory

A new explanation has emerged for why an experimental treatment for Alzheimer’s disease that involves flickering sounds and lights may help slow cognitive decline. This frequency appears to strengthen the brain’s waste processing network, helping to remove beta-amyloid and other toxic proteins that contribute to memory and concentration issues.

“Once we understand the mechanism, we can probably understand how to further optimize this whole concept and improve its effectiveness,” he says. Cai Li Hui at Massachusetts Institute of Technology.

The treatment involves exposure to light that flashes at a frequency of 40 times per second, or 40 hertz, and to a bass sound, also at 40 hertz. Typically, stimulation is given for one hour per day.

The key to this new approach is that large networks of brain cells naturally fire in sync with each other at different frequencies, known as brain waves. Brain waves around 40 Hz are common when people are concentrating and forming or accessing memories.

In 2016, Tsai’s team wondered if 40Hz stimulation could enhance cognitive performance in Alzheimer’s patients, since visual or auditory stimulation at a certain frequency is known to enhance brain waves at that same frequency. I decided to investigate.

Their group and other researchers have shown that this reduces amyloid accumulation in mice with Alzheimer’s disease and has cognitive benefits. Small trial in people with this condition, an even larger trial is underway. However, it is unclear how this treatment works, and another idea is that it boosts the function of immune cells in the brain.

Well, the special light and sound appears to work by enhancing the function of the brain’s drainage system, also known as the glymphatic system.

In the latest study, Tsai’s team conducted a series of experiments to study the mechanism of treatment in mice that were genetically modified to have amyloid buildup that normally occurs with age and to have worse memory than typical mice. carried out.

As expected, when the animals were exposed to light and sound, the amount of amyloid decreased. The new findings were that during treatment, the amount of cerebrospinal fluid entering the brain increased, and the amount of waste fluid leaving the brain through the glymphatic vessels increased.

This appears to occur because nearby blood vessels pulsate more, which may help glymph fluid flow through the blood vessels, allowing more water to flow into the glymph system.

The research team also found that the activity of a particular type of brain cell known as an interneuron appears to cause an increase in glymph flow by releasing a molecule called vasoactive intestinal peptide. When the research team chemically blocked the production of this molecule, the treatment no longer accelerated amyloid clearance.

Miken Nedergaard A professor at the University of Rochester in New York who helped discover the glymphatic system says the discovery is consistent with what we already know about it. “The brain, blood, and cerebrospinal fluid are all contained within the skull. When the blood volume expands, the brain tissue cannot be compressed, so the cerebrospinal fluid volume must also move.”

In the accompanying article natural medicineDr. Nedergaard says that a better understanding of the mechanisms of toxin removal in the brain “could be the key to unlocking that.” [their] Treatment Possibilities.”

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Source: www.newscientist.com

Safeguarding Poison Dart Frogs from Their Lethal Toxins

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Scientists have discovered a “toxin sponge” protein in poison dart frogs that safely stores dangerous alkaloids, offering the possibility of a new approach to treating poisoning in humans. (Artist’s concept) Credit: SciTechDaily.com

The newly identified protein helps poison dart frogs accumulate and store powerful toxins in their skin that they use in self-defense against predators.

Scientists announced that they have identified a protein that helps poison dart frogs safely accumulate their namesake toxin, according to a study published Dec. 19 in the journal Nature. e-life.

The discovery solves a long-standing scientific mystery and could suggest potential therapeutic strategies to treat humans addicted to similar molecules.

Alkaloids: from coffee to frog skin

Alkaloid compounds such as caffeine make coffee, tea, and chocolate delicious and comforting, but they can be harmful if consumed in large amounts. In humans, the liver can safely metabolize moderate amounts of these compounds. Small poison dart frogs ingest far more toxic alkaloids in their diet, but instead of breaking them down, they accumulate them in their skin as a defense mechanism against predators.

“It has long been a mystery how poison dart frogs are able to transport highly toxic alkaloids into their bodies without being poisonous themselves,” said lead author and doctoral student in the Department of Biology at Stanford University in California, USA. Aurora Álvarez Buira says. “We aimed to answer this question by searching for proteins that could bind and safely transport alkaloids in poison dart frog blood.”

Diablito poison dart frog, Uofaga Silvatica, native to Colombia and Ecuador. Credit: Marie-Therese Fischer (CC BY 4.0)

Uncover the secrets of frogs

Alvarez-Buylla and colleagues used compounds similar to poison dart frog alkaloids as a kind of “molecular fishing hook” to attract and bind proteins in blood samples taken from poison dart frogs. The alkaloid-like compounds were bioengineered to glow under fluorescent lights, allowing the researchers to watch proteins bind to the decoys.

They then separated the proteins to see how each protein interacted with the alkaloids in solution. They discovered that a protein called alkaloid-binding globulin (ABG) acts like a “toxin sponge” that collects alkaloids. They also identified how proteins bind to alkaloids by systematically testing which parts of the protein are needed to successfully bind the alkaloids.

Impact on humans and future research

“The way that ABG binds to alkaloids is similar to the way that proteins that transport hormones in human blood bind to their targets,” Álvarez Buira explains. “This finding may suggest that hormone-processing proteins in frogs have evolved the ability to manage alkaloid toxins.”

The authors say the similarities with human hormone transport proteins could be a starting point for scientists to try bioengineering human proteins that “sponge” with toxins. “If successful, these efforts could provide new ways to treat certain addictions,” said lead author Lauren O’Connell, an assistant professor of biology at Stanford University and a member of the Wu Tsai Institute for Neuroscience. he says.

“Beyond potential medical relevance, we have achieved a molecular understanding of a fundamental part of poison dart frog biology, which will inform future research on biodiversity and the evolution of natural chemical defenses.” “This will be important for research,” concludes O’Connell.

Reference: “Binding and isolation of poison dart frog alkaloids” plasma Aurora Alvarez Buira, Marie Therese Fisher, Maria Dolores Moya Garzon, Alexandra E. Rangel, Elisio E. Tapia, Julia T. Tanzo, H. Tom So, Luis A. Coloma, Written by Jonathan Z. Long and Lauren A. O’Connell, December 19, 2023. e-life.
DOI: doi:10.7554/eLife.85096

Funding: National Science Foundation, New York Stem Cell Foundation, National Science Foundation Graduate Research Fellowship Program, Howard Hughes Medical Institute, Alfonso Martín Escudero Foundation, Wu Tsai Human Performance Alliance.

Source: scitechdaily.com