Scientists may now be able to observe the 'tipping point', triggering neurodegenerative diseases: Study

Washington, Feb 16 (PTI) Scientists have developed a new method which was employed to understand how tau protein changes from a benign protein, essential for normal function in human brains, into toxic neurofibrillary tangles.

Such toxic assemblies of tau proteins are a signature of Alzheimer's and other neurodegenerative diseases, and so, this method could allow for its use in understanding the starting point of these diseases, the scientists said.

In this study, the scientists at University of California (UC) Santa Barbara, US, used this method with the core portion, a peptide, of tau.

They were able to observe and analyse a critical "tipping point" between normal, reversible folding and assembly, and the irreversible, pathological assembly that underlies tauopathic, neurodegenerative diseases, the study said.

So far, scientists are not yet clear on how the "tipping point" happens.

This new technique gave the researchers at UC Santa Barbara the ability to control and follow in real time the process by which this critical "tipping point" happens, the study said.

The study appears in the Journal of Biological Chemistry.

According to the study, the technique employed a novel use of low voltage electricity as a surrogate for the natural signals that trigger the protein to fold and assemble, both for its normal function in the brain and in the runaway process leading to often fatal disease.

Employing less than a volt of electrical potential to mimic hyperphosphorylation, the disease-promoting signal, the scientists triggered and finely tuned the tau-peptide's folding in their lab experiments, the study said.

They used spectroscopic methods to reveal details of the folding and progressive assembly to form amyloid-like filaments, the study said.

"This method provides scientists a new means to trigger and simultaneously observe the dynamic changes in the protein as it transitions from good to bad," said Daniel E. Morse, senior author of the study.

"The method should be widely useful to identify molecules and conditions that direct different trajectories of assembly in a number of different but related amyloid diseases," stated Eloise Masqulier, lead author of the interdisciplinary team of students, researchers and faculty from molecular biology, chemistry and engineering.

Unlike other modes of examining protein folding and assembly, such as x-ray diffraction or cryo-electron microscopy that provide static snapshots of the processes as they occur in time, the new electrochemical method allowed users to continuously witness and analyse details of the progressive, dynamical folding and assembly as they occurred in real time, permitting the first direct observations of the critical earliest steps in these processes, the study said.

Also, the study said, unlike most techniques previously used for studies of tau and its core peptide, because the electrical trigger closely mimics the natural triggering signal, the method permits direct observation of these processes without the need for additional "helper" molecules.

The authors reported that the technology could also be used as a tool to more rapidly test and identify drugs and antibodies potentially useful for prevention or treatment of Alzheimer's and other amyloid diseases.

"Because we can turn on and fine-tune the process at will, we can use this system to see what molecules could interdict or block specific stages of folding and assembly," Morse said. PTI KRS KRS KRS