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Bridging the gap between test tube and disease

MAR 22, 2024
A thermodynamics-based framework connects biophysical measurements of protein aggregation to neurodegenerative diseases and potential therapies.
Bridging the gap between test tube and disease internal name

Bridging the gap between test tube and disease lead image

The formation of protein aggregates in the brain is central to many neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Researchers can replicate this process in a test tube to study its biophysical properties. After decades of work, however, it remains difficult to translate biophysical insights into effective therapies for these complex diseases.

Meisl created a framework that draws clear connections between protein aggregation in a test tube and disease.

“Biophysics is such a powerful tool,” said author Georg Meisl. “We cannot afford to neglect it in the search for therapies, so we need better ways of connecting biophysical insights to disease.”

In this thermodynamics-based view of protein aggregation, there is competition between the proteins’ innate drive to aggregate and the removal of aggregates by the organism via energy-consuming processes. Disease occurs when the system bypasses kinetic barriers and these aggregation-removal processes are no longer effective. Recasting protein aggregation in this light suggests that therapies focused on increasing aggregate removal or maintaining aggregate-removal processes may be effective.

This review could be used to examine previous studies, on both the biophysical side and the clinical side, from a new perspective.

“The hope is that this will help researchers on the disease side to better understand which therapeutic targets our biophysical understanding highlights as most useful, as well as help biophysicists to design and interpret their studies more easily in the context of disease,” Meisl said.

Meisl believes the field must develop models that can predict how modifications in aggregation behavior alter characteristics of neurodegenerative diseases. These models could be used in drug development to discover therapeutic molecules through biophysical assays in test tube experiments.

Source: “The thermodynamics of neurodegenerative disease,” by Georg Meisl, Biophysics Reviews (2024). The article can be accessed at https://doi.org/10.1063/5.0180899 .

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