Medical News - Alzheimer's Breakthrough

Two stories caught my attention this weekend. I tend to believe that these are going to accelerate as AI is applied. No idea if these are the result of utilizing AI but on 60 minutes tonight they mentioned that AI had now decoded every known protein and did it in relatively short time. For comparison, they said t would take a PhD student 2 years to do a single protein.

Google's DeepMind AI Predicts 3D Structure of Nearly Every Protein Known to Science - CNET

After 22 years of grueling experimentation, John Kendrew of Cambridge University finally uncovered the 3D structure of a protein. It was a twisted blueprint of myoglobin, the stringy chain of 154 amino acids that helps infuse our muscles with oxygen. As revolutionary as this discovery was, Kendrew didn't quite open up the protein architecture floodgates. During the next decade, fewer than a dozen more would be identified.

Fast-forward to today, 65 years since that Nobel Prize-winning breakthrough.

On Thursday, Google's sister company, DeepMind, announced it has successfully used artificial intelligence to predict the 3D structures of nearly every catalogued protein known to science. That's over 200 million proteins found in plants, bacteria, animals, humans — almost anything you can imagine.

"Essentially, you can think of it as covering the entire protein universe," Demis Hassabis, founder and CEO of DeepMind, told reporters this week.

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One story of significance is discovery of a peptide by MIT researchers that reversed the effect of alzheimers in mice.

MIT Scientists Reveal ‘Remarkable’ Breakthrough For Treating Alzheimer’s (msn.com)

Neuroscientists at MIT have discovered a way to potentially reverse neurodegeneration and other issues related to Alzheimer’s disease, according to a news release from the school.

Researchers, experimenting on mice, found that interfering with an enzyme that is typically overactive in the brains of people with Alzheimer’s can reverse the degeneration in the brain.

The neuroscientists treated the mice with a peptide that successfully blocked the hyperactive version of enzyme CDK5 and found that it resulted in heavy reductions in the neurodegeneration and DNA damage taking place inside the brain.

Researchers found that the peptide leads to a moderate reduction in CDK5 activity while not interfering with the normal CDK5-P35 complex. When the team tested the peptide in a mouse model of Alzheimer’s disease caused by hyperactive CDK5, they found many beneficial results, including reductions in DNA damage, neural inflammation, and neuron loss.

 

second story which was even more fascinating to me was the discovery within the human genome long dormant virus that when activated, causes the body to elicit an immune response to lung cancer and they suspect that it can be used to help create cures or vaccines for cancers of all types. perhaps our bodies ahve the ability to cure all sorts of diseases that plague us and we just need to understand how to unlock the potential

Stowaways in the genome: Thousands of unknown viruses hide in the DNA of unicellular organisms -- ScienceDaily

At the University of Innsbruck, scientists have discovered over 30,000 viruses by using the high-performance computer cluster "Leo" and sophisticated detective work. The viruses hide in the DNA of unicellular organisms. In some cases, up to 10% of microbial DNA consists of built-in viruses.
During a large-scale study of complex single-celled microbes, Dr. Christopher Bellas, Marie-Sophie Plakolb and Prof. Ruben Sommaruga from the Department of Ecology at the University of Innsbruck made an unexpected discovery. Built into the genome of the microbes, they found the DNA of over 30,000 previously unknown viruses. This "hidden" DNA may allow the replication of complete and functional viruses in the host cell.

"We were very surprised by how many viruses we found through this analysis," says Bellas. "In some cases, up to 10% of a microbe's DNA turned out to consist of hidden viruses." These viruses do not appear to harm their hosts. On the contrary, some may even protect them. Many appear to be similar to so-called virophages. These viruses infect and destroy other, harmful viruses that infect their host cell.
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From bacteria to humans, all life forms are continuously infected with viruses. Some are constantly present, but only occasionally trigger symptoms, such as the herpes virus in humans. Others hide even deeper, becoming part of their host's DNA. This study found that many of the Earth's abundant single-celled eukaryotic (complex) organisms are packed with viruses. These organisms are found everywhere, and include abundant algae in lakes and oceans, amoebae in soil, as well as human parasites.

"Why so many viruses are found in the genomes of microbes is not yet clear," says Bellas. "Our strongest hypothesis is that they protect the cell from infection by dangerous viruses." Many eukaryotic single-celled organisms are infected by "giant viruses," a group of viruses that can be as large as bacteria. These infections kill the host as they create new copies of the giant virus. However, when a virophage resides in the host cell, it 'reprograms' the giant virus to build virophages. As a result, the giant virus can sometimes be fended off and the host cell population is saved from destruction.

Targeting ‘viral footprints’ in our DNA could boost cancer treatment | Crick

The research team in collaboration with scientists at UCL, set out to understand the link between better responses to immunotherapy and the presence of antibody-producing B cells around the perimeter of a tumour. They investigated immune cell activity in mice with lung cancer and also in tumour samples from people with lung cancer collected as part of the Cancer Research UK funded TRACERx study. They found that B cells contribute to the immune response to lung cancer through the production of tumour-binding antibodies, in a manner similar to how B cells produce anti-viral antibodies following flu or SARS-CoV-2 vaccination.

When they investigated the target of this immune response, they found that these antibodies recognised proteins expressed by ancient viral DNA, called endogenous retroviruses (ERVs). This viral DNA makes up around 5% of the human genome, passed down from the historic infections of our ancestors. The viral genes are silenced in the majority of healthy tissue, but in cancers they can be woken up.

Katey Enfield, postdoctoral training fellow at the Crick and joint first author with PhD students Kevin Ng and Jesse Boumelha, said: “There is a huge focus on the activity of T cells against cancer because of their ability to destroy tumour cells. But our work highlights an important role for antibody responses and also how these responses might be boosted with immunotherapy.
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George Kassiotis, head of the Retroviral Immunology Laboratory at the Crick, said: “ERVs have been hiding as viral footprints in the human genome for thousands or millions of years so it’s fascinating to think that the diseases of our ancestors might be key to treating diseases today. “With more research, we could look to develop a cancer treatment vaccine made up of activated ERV genes to boost antibody production at the site of patient’s cancer and hopefully improve the outcome of immunotherapy treatment.”


here is the technical paper for those smart enough to decipher it

Antibodies against endogenous retroviruses promote lung cancer immunotherapy | Nature

 

New research claiming that Tau clumps prevent neurons from turning off stress switch and that is what leads to cell death and dimentia. Treat the on/off switch to function properly and cells don't die.

Dementia breakthrough "changes how we think" about treatment

Most research into treatments focused on breaking up these clumps has shown little success. But new research by Rapé's lab, published in the journal Nature, suggests that these protein accumulations may not actually be responsible for killing our brain cells. Rather, it appears the brain cells are dying due to the body's own failure to turn off their stress response.
"We now found that aggregates prevent silencing of a stress response that cells originally mount to cope with bad proteins," Rapé said. "The stress response is always on, and that's what kills the cells."
Aggregates don't kill cells directly," he said. "They kill cells because they keep the light on. But that means that you can treat these diseases, or at least the dozen or so neurodegenerative diseases that we found have kept their stress responses on. You treat them with an inhibitor that turns off the light. You don't have to worry about completely getting rid of large aggregates, which changes how we think about treating neurodegenerative diseases. And most importantly, it makes this really doable."
Key to the team's discovery was a large protein complex which they called Silencing Factor of the Integrated stress response, aka SIFI. This molecular machine serves two main purposes: first it cleans up the abnormal protein clumps and, when it's done, it switches off the brain cells' stress response, mounted to cope with the abnormal proteins.