Lifespan.io reports that researchers have reduced memory and learning symptoms in mice. Alzheimer’s research needs new approaches. A paper describes a promising molecule built using a technique that can be expanded to numerous other proteins with post-translational modifications. The researchers were also able to deliver the rather large molecule intranasally across the blood-brain barrier, alleviating symptoms of Alzheimer’s. However, murine models of Alzheimer’s are not completely adequate.
Recent progress in the field of targeted protein degradation (TPD) has proven its immense potential as a novel therapeutic modality in drug discovery. In 2015, Bradner and his colleagues devised a phthalimide-based small molecule that promotes degradation of transcriptional coactivator BRD4 by hijacking the Cereblon (CRBN) E3 ubiquitin ligase complex.
In the same year, Crews and his colleagues also reported a TPD technology recruiting the von Hippel–Lindau (VHL) E3 ligase complex, commonly referred to as proteolysis-targeting chimeras (PROTACs).
These technologies feature bifunctional small molecules that bring the proteins of interest into proximity with the E3 ubiquitin ligase complexes for ubiquitination and subsequent proteasomal degradation.
Such TPD-based small molecules have several advantages over traditional small molecule inhibitors in that they eliminate the target protein instead of modulating its function.
TPD technology thus can complement nucleic acid-based gene knockdown in removing unwanted intracellular proteins. In addition, the TPD technique can target a plethora of proteins in various compartments of the cell, including disease-causing proteins that have previously been considered undruggable with the conventional small-molecule approach. Recently, several strategies have been suggested to potentiate therapeutic efficacy of TPD technology.
In particular, TPD molecules that recognize and bind to the protein with specific post-translational modifications (PTMs), such as phosphorylation, may be a novel strategy to induce selective degradation of pathological proteins attributed to aberrant PTMs.
However, a TPD molecule specifically targeting post-translationally modified proteins has not been reported yet.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
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Who the phuck cares about mice? Find something to help people, now!!
And if old folk start dying you will cry “Why didn’t they test it first?!”
Why does everyone work so hard to avoid saying benfotiamine is the most cost-effective chemopreventative for Alzheimer’s?
Could it be because benfotiamine is not under patent, doesn’t deliver exclusive economic rents to investors and thus can’t provide campaign donations to crooked politicians?
Benfotiamine blocks phosphorylation of p38MAPK.
There were theoretical indications as far back as 2005 that benfotiamine would be effective for Alzheimer’s. The evidence became undeniable by 2016. You would have thought for all the talk on TV about how much people “cared” about treating Alzheimer’s everyone would have rushed out to use it .
Of course, the same is true for the benefits of ketogenic diets, which we’ve ignored. Gee. Who pays for the “news” in this country? Two-thirds of the ad buys on the news are for-profit medicine of various sorts and then the processed food that helps cause insulin-resistant conditions like Alzheimer’s make up part of the remainder.
Interesting. Looking up some NHI research on the topic, I see that it does show some promise.
Best of all, it’s OTC, and has a low risk profile! And isn’t terribly expensive.
I might just start taking it as a low risk preventative, thanks!
Been taking it for a few years. It also has activity against Advanced Glycation End-products.
Your theory explains too much.
There are no monopoly profits for the off-patent preventative medicine of diet, exercise, daily aspirin, sunscreen, condoms (if indulging in promiscuous sex) etc. etc. Yet all these things are widely promoted by health authorities.