February 23, 2023
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Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities. They stress that this was a small sample of mice and that human testing is far off, but believe the result indicates that within a decade, their synthetic molecule could be developed into a drug for treating the degenerative disease. The peer-reviewed research, led by neuroscientists from Ben-Gurion University, was recently published in the journal Translational Neurodegeneration.
“We are taking a very different approach than efforts at Alzheimer’s medicines that we have seen so far,” Prof. Varda Shoshan-Barmatz, the lead author, told The Times of Israel. “Most are trying to address plaque that forms in the brain, but we are addressing dysfunction elsewhere. And we’re optimistic. Mice who had Alzheimer’s and received our molecule and then underwent tests had the same cognitive abilities as mice who’d never had Alzheimer’s.”
Interestingly, the molecule appears to have been effective without significantly reducing the amount of plaque, which she thinks indicates that scientists may have been overly fixated on the plaque. There is scientific literature on the dysfunction of mitochondria among people with Alzheimer’s. Mitochondria are organelles — tiny miniature organs within cells — that provide the cell with power. Scientists believe that when they malfunction and fail to produce the normal quantities of energy, it can lead to cell death, inflammation and reduced immune response.
Despite Alzheimer’s being linked to mitochondrial dysfunction, no drug candidates are currently focused on mitochondria. Drug research is mostly concerned with combatting the buildup of protein fragments between nerve cells in the brain, which are thought to be linked to Alzheimer’s. The Ben-Gurion University team set out to normalize mitochondrial activity by countering the harmful effects that occur when a protein called VDAC1 is over-produced. The protein plays a crucial role in regulating the metabolic and energetic functions of mitochondria when produced in normal quantities. But the scientists found that it is produced in huge levels in the brains of mice with Alzheimer’s, and interferes with mitochondrial activity.
“In our research, we have shifted the focus of Alzheimer’s treatments from the plaque to this protein, which is produced in the nerve cells around the plaque instead,” said Shoshan-Barmatz. “We prevent this protein from causing cell death, as the molecule interferes with its harmful effect.”
Source: https://in.bgu.ac.il/
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https://www.timesofisrael.com/
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Tags: Alzheimer's, artificial molecule, Ben-Gurion University, brain, cell, cognitive abilities, degenerative disease, drug, immune response, inflammation, mitochondria, nerve cells, organelles, plaque, protein, Translational Neurodegeneration, VDAC1
October 27, 2022
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A topical gel that blocks the receptor for a metabolic byproduct called succinate treats gum disease by suppressing inflammation and changing the makeup of bacteria in the mouth, according to a new study led by researchers at NYU College of Dentistry and published in Cell Reports. The research, conducted in mice and using human cells and plaque samples, lays the groundwork for a non-invasive treatment for gum disease that people could apply to the gums at home to prevent or treat gum disease.
Gum disease (also known as periodontitis or periodontal disease) is one of the most prevalent inflammatory diseases, affecting nearly half of adults 30 and older. It is marked by three components: inflammation, an imbalance of unhealthy and healthy bacteria in the mouth, and destruction of the bones and structures that support the teeth. Uncontrolled gum disease can lead to painful and bleeding gums, difficulty chewing, and tooth loss.
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| Tags: bacteria, bone loss, dental plaque, gel, gum, human cells, inflammation, mouth, NYU College of Dentistry, NYU Dentistry, periodontitis, plaque, succinate
June 7, 2022
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Karina Gasbarrino, a McGill University PhD graduate has dedicated her career to enhancing the early prediction and prevention of strokes, and she created a tool that uses artificial intelligence (AI) that does just that. This week, her work won her the Mitacs Social Entrepreneurship Award, a national innovation award presented to an applicant whose start-up works to address or solve social, cultural or humanitarian issues. Gasbarrino said this recognition means a lot to her, as she chose to delve into this kind of research based on a personal experience.
Harmful fatty deposits in the arteries of the neck, called plaques, are the main cause of strokes when ruptured
“It really started off because we have a family history of cardiovascular disease,” Gasbarrino said. “I ended up losing my grandfather over 10 years ago due to a stroke.” “It was really instantaneous, like one minute he was here, the next he was not. And so that really impacted me and my family and it gave me the drive to want to go into research and really understand what causes these strokes and how we could better predict and prevent them.”
Gasbarrino is the co-founder and COO of digital health start-up PLAKK, a software which uses image analysis technology to more accurately examine harmful fatty deposits in the arteries of the neck, called plaques, which, when ruptured, are the main cause of strokes. “What we’re trying to do with our technology is provide clinicians with more information about those plaques … and by understanding that, we can better determine whether a patient is at risk of having a stroke,” she said.
According to Gasbarrino, as it stands, there is no blood test that can used to detect plaques in the neck artery. Imaging is required, but even then, there’s no tool to determine what that plaque is composed of or how dangerous it is. “That’s why we’re developing the technology,” she said. “We want to be able to intervene and get patients the treatment that they need before they end up having a stroke.”
The tool is currently in the validation phase and the team is working to get regulatory approval in the coming six months. The hope is to have the technology implemented in a few centres across Canada as well as some in the U.S. by early 2023. Gasbarrino said the development of this technology would not have been possible without the support of her PhD supervisor, Dr. Stella S. Daskalopoulou, a clinician-scientist at the Montreal University Health Centre, as well as Kashif Khan, another recent PhD graduate from McGill University involved in the project.
Source: https://www.cbc.ca/
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| Tags: AI, Artificial Intelligence, Karina Gasbarrino, McGill University, Mitacs Social Entrepreneurship Award, neck artery, PLAKK, plaque, stroke
March 23, 2021
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A two-week course of high doses of CBD helps restore the function of two proteins key to reducing the accumulation of beta-amyloid plaque, a hallmark of Alzheimer’s disease, and improves cognition in an experimental model of early onset familial Alzheimer’s, investigators report. The proteins TREM2 and IL-33 are important to the ability of the brain’s immune cells to literally consume dead cells and other debris like the beta-amyloid plaque that piles up in patients’ brains, and levels of both are decreased in Alzheimer’s.
The investigators report for the first time that CBD normalizes levels and function, improving cognition as it also reduces levels of the immune protein IL-6, which is associated with the high inflammation levels found in Alzheimer’s, says Dr. Babak Baban, immunologist and associate dean for research in the Dental College of Georgia (DCG) and the study’s corresponding author. There is a dire need for novel therapies to improve outcomes for patients with this condition, which is considered one of the fastest-growing health threats in the United States, DCG and Medical College of Georgia (MCG) investigators write in the Journal of Alzheimer’s Disease.
“Right now we have two classes of drugs to treat Alzheimer’s,” says Dr. John Morgan, neurologist and director of the Movement and Memory Disorder Programs in the MCG Department of Neurology. “One class increases levels of the neurotransmitter acetylcholine, which also are decreased in Alzheimer’s, and another works through the NMDA receptors involved in communication between neurons and important to memory. But we have nothing that gets to the pathophysiology of the disease,” says Morgan, a study coauthor.
The DCG and MCG investigators decided to look at CBD’s ability to address some of the key brain systems that go awry in Alzheimer’s.
They found CBD appears to normalize levels of IL-33, a protein whose highest expression in humans is normally in the brain, where it helps sound the alarm that there is an invader like the beta-amyloid accumulation. There is emerging evidence of its role as a regulatory protein as well, whose function of either turning up or down the immune response depends on the environment, Baban says. In Alzheimer’s, that includes turning down inflammation and trying to restore balance to the immune system, he says.
CBD also improved expression of triggering receptor expressed on myeloid cells 2, or TREM2, which is found on the cell surface where it combines with another protein to transmit signals that activate cells, including immune cells. In the brain, its expression is on the microglial cells, a special population of immune cells found only in the brain where they are key to eliminating invaders like a virus and irrevocably damaged neurons.
Source: https://jagwire.augusta.edu/
Categories: Uncategorized
| Tags: Alzheimer's, beta-amyloid plaque, brain’s immune cells, cannabis, CBD, cells, cognition, DCG, Dental College of Georgia, IL-33, immune cells, immune protein IL-6, MCG, Medical College of Georgia, microglial cells, NMDA receptors, plaque, proteins, TREM2
May 4, 2020
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People who are affected by Alzheimer’s disease have a specific type of plaque, made of self-assembled molecules called β-amyloid (Aβ) peptides, that build up in the brain over time. This buildup is thought to contribute to loss of neural connectivity and cell death. Researchers are studying ways to prevent the peptides from forming these dangerous plaques in order to halt development of Alzheimer’s disease in the brain.
In a multidisciplinary study, scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory, along with collaborators from the Korean Institute of Science and Technology (KIST) and the Korea Advanced Institute of Science and Technology (KAIST), have developed an approach to prevent plaque formation by engineering a nano-sized device that captures the dangerous peptides before they can self-assemble.
Transmission Electron Microscopy (TEM) images of Aβ peptide samples in the presence of the Aβ nanodevices (scale bar: 200 nm). The lack of grains in the image indicates the effectiveness of the nanodevice in trapping the peptides
We’ve taken building blocks from nanotechnology and biology to engineer a high-capacity cage’ that traps the peptides and clears them from the brain.” — Elena Rozhkova, scientist, Center for Nanoscale Materials
The β-amyloid peptides arise from the breakdown of an amyloid precursor protein, a normal component of brain cells,” said Rosemarie Wilton, a molecular biologist in Argonne’s Biosciences division.In a healthy brain, these discarded peptides are eliminated.”
In brains prone to the development of Alzheimer’s, however, the brain does not eliminate the peptides, leaving them to conglomerate into the destructive plaques.
The idea is that, eventually, a slurry of our nanodevices could collect the peptides as they fall away from the cells — before they get a chance to aggregate,” added Elena Rozhkova, a scientist at Argonne’s Center for Nanoscale Materials (CNM), a DOE Office of Science User Facility.
Source: https://www.anl.gov/
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| Tags: Alzheimer's, Argonne National Laboratory, Argonne’s Center for Nanoscale Materials, brain, KAIST, KIST, Korea Advanced Institute of Science and Technology, Korean Institute of Science and Technology, molecules, nanotechnology, plaque, β-amyloid (Aβ) peptides
January 28, 2020
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A drug-coated nanoparticle reduces plaque buildup in mouse arteries without causing harmful side effects, researchers have found.
Atherosclerosis, the accumulation of plaque inside artery walls, can lead to heart attacks and strokes. It’s the world’s No. 1 killer. Available therapies treat risk factors such as high blood pressure and high cholesterol but fail to address the accumulation of diseased cells and inflammation within artery walls.
“This is precision medicine,” said Nicholas Leeper, MD, professor of vascular surgery and cardiovascular medicine. “We used the nanotubes to deliver a payload like a Trojan horse.”
Leeper, who sees patients at Stanford Health Care’s vascular and endovascular care clinic, is a senior author of a paper about the research that was published Jan. 27 in Nature Nanotechnology. The other senior author is Bryan Smith, PhD, a former visiting associate professor at the School of Medicine. He is now an associate professor of biomedical engineering at Michigan State University.
Source: http://med.stanford.edu/
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| Tags: artery walls, atherosclerosis, cholesterol, diseased cells, Heart attacks, high blood pressure, inflammation, Michigan State University, nanoparticle, Nanotherapy, plaque, Stanford School of Medicine, strokes
December 11, 2019
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Heart disease and stroke are the world’s two most deadly diseases, causing over 15 million deaths in 2016 according to the World Health Organization. A key underlying factor in both of these global health crises is the common condition, atherosclerosis, or the build-up of fatty deposits, inflammation and plaque on the walls of blood vessels. By the age of 40, around half of us will have this condition, many without symptoms.
A new nanoparticle innovation from researchers in USC Viterbi’s Department of Biomedical Engineering may allow doctors to pinpoint when plaque becomes dangerous by detecting unstable calcifications that can trigger heart attacks and strokes. The research — from Ph.D. student Deborah Chin under the supervision of Eun Ji Chung, the Dr. Karl Jacob Jr. and Karl Jacob III Early-Career Chair, in collaboration with Gregory Magee, assistant professor of clinical surgery from Keck School of Medicine of USC — was recently published in the Royal Society of Chemistry’s Journal of Materials Chemistry B on 25 September 2019.
When atherosclerosis occurs in coronary arteries, blockages due to plaque or calcification-induced ruptures can lead to a clot, cutting blood flow to the heart, which is the cause of most heart attacks. When the condition occurs in the vessels leading to the brain, it can cause a stroke.
A MICROSCOPIC VIEW OF ATHEROSCLEROSIS IN A PULMONARY ARTERY
“An artery doesn’t need to be 80 percent blocked to be dangerous. An artery with 45% blockage by plaques could be more rupture-prone,” Chung said. “Just because it’s a big plaque doesn’t necessarily mean it’s an unstable plaque.”
Chung said that when small calcium deposits, called microcalcifications, form within arterial plaques, the plaque can become rupture prone. However, identifying whether blood vessel calcification is unstable and likely to rupture is particularly difficult using traditional CT and MRI scanning methods, or angiography, which has other risks.
“Angiography requires the use of catheters that are invasive and have inherent risks of tissue damage,” said Chin, the lead author. “CT scans on the other hand, involve ionizing radiation which can cause other detrimental effects to tissue.”
Source: https://viterbischool.usc.edu/
Categories: Uncategorized
| Tags: angiography, atherosclerosis, blockages, brain, calcification, clot, coronary arteries, fatty deposits, Heart attacks, heart disease, inflammation, Keck School of Medicine, microcalcifications, nanoparticle, plaque, stroke, University of South California, USC, USC Viterbi
August 13, 2018
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Combine a diet high in sugar with poor oral hygiene habits and dental cavities, or caries, will likely result. The sugar triggers the formation of an acidic biofilm, known as plaque, on the teeth, eroding the surface. Early childhood caries is a severe form of tooth decay that affects one in every four children in the United States and hundreds of millions more globally. It’s a particularly severe problem in underprivileged populations.
Treatment with a nanoparticle and hydrogen peroxide (right panel) left little in the way of bacteria (in blue) or the sticky biofilm matrix (in red), making the combination a potent force against dental plaque
In a study published in Nature Communications, researchers led by Hyun (Michel) Koo of the University of Pennsylvania School of Dental Medicine in collaboration with David Cormode of Penn’s Perelman School of Medicine and School of Engineering and Applied Science used FDA-approved nanoparticles to effectively disrupt biofilms and prevent tooth decay in both an experimental human-plaque-like biofilm and in an animal model that mimics early-childhood caries. The nanoparticles break apart dental plaque through a unique pH-activated antibiofilm mechanism.
“It displays an intriguing enzyme-like property whereby the catalytic activity is dramatically enhanced at acidic pH but is ‘switched off’ at neutral pH conditions,” says Koo, professor in Penn Dental Medicine’s Department of Orthodontics. “The nanoparticles act as a peroxidase, activating hydrogen peroxide, a commonly used antiseptic, to generate free radicals that potently dismantle and kill biofilms in pathological acidic conditions but not at physiological pH, thus providing a targeted effect.”
Because the caries-causing plaque is highly acidic, the new therapy is able to precisely target areas of the teeth harboring pathogenic biofilms without harming the surrounding oral tissues or microbiota. The particular iron-containing nanoparticle used in the experiments, ferumoxytol, is already FDA-approved to treat iron-deficiency, a promising indication that a topical application of the same nanoparticle, used at several-hundred-fold lower concentration, would also be safe for human use.
Source: https://penntoday.upenn.edu/
Categories: Uncategorized
| Tags: biofilms, caries, dental cavities, FDA-approved, ferumoxytol, microbiota, nanoparticles, oral hygiene, Penn’s Perelman School of Medicine, plaque, sugar, tissue, unique pH-activated antibiofilm, University of Pennsylvania School of Dental Medicine
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