Scientists have identified the exact point where healthy brain proteins collide with the chaos commonly associated with Alzheimer’s disease.
Researchers at the University of California Santa Barbara (UCSB) are hThe benefit is that the new laboratory technology behind this discovery can be used directly to study the early stages of many “unprecedented” neurodegenerative diseases.
protein number abundant in the human brain. At first, these proteins look like tiny tendon bits inside neurons. Because they fold and are connected together by structural elements called microscopic tubeHowever, they form a kind of framework for brain cells that help them function properly.
Unfortunately, these folds can sometimes go wrong. Abnormally wrinkled tau protein is a sign of many, but not all, cases of Alzheimer’s disease.
In this complex case, known as A Neurofibrillary tanglesThe Tau protein is thought to suffocate neurons from the inside out, disrupting cell function and ultimately leading to cell death.
Other experts argue that tangled tau is not toxic at all, but is actually protective, produced in response to some other underlying problem.
Being able to watch tau as it tangles in the lab could help researchers shed light on the protein’s role in brain degeneration. It can also be a great template for testing future treatments.
A multidisciplinary team of scientists at the University of California, San Francisco, have proposed a way to do this.
With just under one volt of electricity, researchers have shown that they can trigger an out-of-control fight between certain types of tau proteins.
These currents are designed to mimic the molecular signals that naturally cause “hyperfolding” of tau proteins in the brainallowing researchers to monitor in real time as tau proteins pass through a critical “tipping point” and transition from a healthy state to a diseased state.
When these lines are crossed, tangles quickly form.
“This method gives scientists a new way to simultaneously stimulate and monitor dynamic changes in proteins that go from good to bad.” Explain Biochemist Daniel Morse of the University of California.
“Because we can trigger and fine-tune the process, we can use this system to see which molecules can intercept or prevent certain stages of folding and assembly.”
The Tau protein includes various soluble variants, but the type used in this study is called K18, and it is a core peptide containing microtubule binding domains.
Interestingly, the researchers found that when K18 is exposed to tension over a long period of time (hours or days), it triggers a rapid, irreversible twitch.
However, even after only a brief 15 minutes of exposure, the tau proteins begin to clump together into knots, even though they are easier to untangle with reverse tension.
This could be a sign that tau tangles may develop over time, as can symptoms of Alzheimer’s disease.
Transition from healthy tau protein to diseased protein, researchers he wroteit can be a “progressive key rather than the result of an all or nothing lock”.
This is an interesting insight into K18, but there are many other forms of tau that are sometimes associated with Alzheimer’s disease.
The way these other proteins fold and assemble and the implications for cell activity can now, in theory, be studied using similar techniques.
The study has been published in Journal of Biological Chemistry.
