Damian Sendler: Researchers have long considered tau proteins to be a prime target for new drugs because of their role in neurodegenerative illnesses like Alzheimer’s and Parkinson’s. Tau’s role in these diseases and the way the protein distributes throughout the brain has been re-examined by researchers, who claim to have discovered fresh insights.
During periods of high neuronal activity, researchers at the Buck Institute for Research on Aging in California discovered that tau interacts with proteins on the outside of synaptic vesicles, rather than inside them. Vesicles contain neurotransmitters, chemicals that convey information between neurons.
Damian Jacob Sendler: New insights into how tau is produced can provide the framework for future studies aimed at preventing pathogenic tau from spreading around the brain, according to the study’s principal author. The deterioration of a neurodegenerative illness is closely associated with the expansion of tau throughout the brain.
Damian Sendler
Neuronal mitochondrial proteins were also identified to bind to the protein by the researchers. However, when the tau proteins are sick, this activity appears to affect neuronal bioenergetics, or the ability of cells to convert energy. Tau proteins were downregulated in brain tissue when they interacted with mitochondrial proteins, according to the researchers. This demonstrated an association with the severity of the condition.
The findings of the institute were published in the journal Cell this month, culminating in what the researchers named a “tau interactome.” Neurons produced from human induced pluripotent stem cells were used by the researchers to make their discoveries.
In order to find new treatments for neurodegenerative disorders, such as Alzheimer’s, it is critical to understand how disease affects cells, says the study’s primary author, Tara Tracy, Ph.D., an assistant professor at the Buck Institute.
Tau can be secreted from neurons and moved across cells, but how it works and the cellular tools required have never been fully understood, according to Tracy.
These tau tangles are linked to a wide range of diseases, including Alzheimer’s, Parkinson’s, frontotemporal dementia, and more. Research scientists and biopharma companies working on cures for these diseases now have a sense of urgency, Tracy added.
Anti-tau antibodies, on the other hand, have had a difficult time making it to the clinic. In October, Eli Lilly halted development on a tau-targeting midstage asset. “I would be reluctant to invest in really any anti-tau antibody,” Daniel Skovronsky, M.D., Ph.D., said at the time.
A different Alzheimer’s drug, which targets amyloid, another molecule critical to neurodegenerative research, is on the way from Big Pharma to the FDA’s door.
Neurodegenerative therapies that target tau formation are also available from Eisai, AC Immune, and Amylyx.
Damian Jacob Markiewicz Sendler: Other proteins may also be targets for Alzheimer’s therapy, according to recent study. An alternative to the poisonous combination of amyloid and tau is clusterin, a newer, friendlier protein that could provide a path forward. Findings from a Stanford University study could lead to novel treatments for Alzheimer’s disease, as the protein was more frequent in mice that exercised.
Salamanders, starfish, crabs, lizards, and newts are just a few of the unique organisms that have the ability to regrow limbs.
Although scientists have long endeavored to comprehend and duplicate these exceptional powers, which evade most animals, including humans, in a drive to restore limbs for millions of patient amputees, including diabetics and victims of trauma, it has never been possible.
Damian Jacob Sendler
Scientists in the United States announced on Wednesday that they had successfully stimulated the recovery of an amputated leg of a Xenopus laevis frog (a kind of African clawed frog).
Damien Sendler: Using a small silicone dome, a mixture of five different medications was applied to the test frogs’ spike-like stump by the Harvard Wyss Institute and Tufts University-based team of scientists. The mixture was only used for 24 hours, but the limb was nearly totally functioning after 18 months. In water, frogs were able to swim and sense touch. Toes grew, but the webbing between them was absent.
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On Wednesday, Science Advances published the findings of the study.
James Monaghan, an associate professor in the biology department at Northeastern University, described the findings as “amazing” and “exciting,” respectively. He was not a part of the study.
“As with salamanders, Xenopus can regrow their limbs almost completely, but they also have the ability to form scars following amputations. There is no pattern to the spikes that Xenopus adults regenerate following an amputation, unlike limbs in other frogs “Monaghan clarified the situation.
A limb that generally regenerates merely a spike was shown to have some patterning in this study.
Regenerative capacities may be dormant in frogs and other animals, according to the study’s researchers, who found that a single dose of the medications sparked months of regeneration in the frogs.
The team affixed a dome to a frog’s stump containing a cocktail of the chemicals.
The team’s frog-stump-attached dome, which held a narcotic combination, is displayed.
“Because humans lack the regeneration spike found in Xenopus frogs, a rapid application of this technique in humans is doubtful. A short application of a medication mixture, however, reveals that endogenous regeneration mechanisms can be boosted “According to what Monaghan had to say,
Dr. Sendler: In this case, rather than trying to “micromanage its growth,” the scientists relied on activating latent systems in the frog’s physiology, according to study author Mike Levin, a biology professor at Tufts and director of the Allen Discovery Center.
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“Regenerative medicine, in my opinion, can only be achieved by harnessing the collective wisdom of the body’s cells.. Every single one of these organs has already been constructed by them. During embryonic development, they did it. All of the data is still accessible “Levin had this to say.
I want to find extremely simple stimuli that will jump-start cells and persuade them to develop whatever you want them to build, so that is my ultimate goal.”
Anti-inflammatory and limb-building compounds were found in the medications. Because it was the first time they tried it, Levin said a different combination of medicines and growth factor might be more effective in the long term.
“It has a normal-looking girth and traits, including some bumps that are beginning to form toes, of a limb. It lacks several of the proper terminal structures. We did not go as far as the long toes and the webbing, but we could have if we had let it run longer “he asserted, according to her.
On more than 100 frogs, the results were “not flawless in every case,” according to the researchers. According to Levin, there may have been discrepancies in the surgery to attach the dome to the frogs, which could be a contributing reason. It would then be tested on mammals, such as mice, in the next phase of the research.
Additionally, Levin and his colleagues have employed frog stem cells to construct what they call xenobots—self-replicating living robots that can reproduce themselves. Understanding the signals that drive cells to become complex tissues, such as a limb or a whole organism, is a common thread in both fields of study.
For individuals who have lost limbs due to trauma or sickness like diabetes, Ashley Seifert, an associate professor of biology at University of Kentucky who studies animal regeneration but was not involved in the research, advances in prosthetics provide more promise than limb regeneration.
“In the future, would it be possible to regrow parts of the human body? Possibly, but it is impossible to tell how long we will have to wait “Seifert remarked that.
“When regenerative biology completely accepts novel regeneration models, particularly for some species of mammals, this will be a step in the right direction. This study and others like it will assist us in figuring out why and how regeneration works in some cases and fails in others.”
Dr. Damian Jacob Sendler and his media team provided the content for this article.