Proteins ensure that human cells function and are viable. Proteins are formed to perform a specific task in the cell and once this task has been completed, they are broken down again. If this process is disrupted, diseases such as Parkinson’s or Alzheimer’s can develop.
Both diseases are characterized by the destruction of nerve cells in the brain and are therefore referred to as neurodegenerative diseases. While Parkinson’s disease leads to movement disorders such as trembling, slowed movements, balance problems and stiffened muscles, Alzheimer’s disease manifests itself in increasing memory problems and perceptual disorders, among other things.
In both cases, the cause is that old and damaged proteins are not broken down properly, accumulate in the cells and clump together. These protein clumps, also known as aggregates, can no longer be broken down by the body, and they ensure that the nerve cells are gradually destroyed.
In an international collaboration involving the University Medical Center Göttingen (UMG), Dr. Eugenio F. Fornasiero, group leader at the UMG’s Department of Neuro- and Sensory Physiology, and his U.S. colleagues from Yale University in New Haven, Connecticut, and St. Jude Children’s Research Hospital in Memphis, Tennessee, have produced the most complete map to date of how long different proteins persist in many tissues of the body.
“This extensive data set is like a blueprint for understanding how different organs manage their proteins,” says Dr. Fornasiero, one of the study’s last authors. “We can see which proteins are turned over quickly in the brain, for example, and which ones persist longer—this gives us clues about their stability and their role in neurodegenerative diseases.”
The researchers discovered that a mechanism that switches proteins “on” and “off” also plays a role in the stabilization of proteins: protein phosphorylation. In this process, phosphate groups are transferred to proteins, which leads to the corresponding protein being switched on, i.e., activated. Removing the phosphate groups switches the protein off.
In the brain tissue of mice suffering from Alzheimer’s disease, for example, the scientists were able to show that the protein “Tau,” which is involved in the development of the disease, is increasingly phosphorylated in certain sections. This increases the stability of the Tau protein and prolongs its lifespan. This in turn promotes the formation of protein aggregates and the death of nerve cells.
“Understanding how phosphorylation influences the stability and turnover of proteins could help to develop new therapeutic strategies for the treatment of Parkinson’s and Alzheimer’s disease. For example, by preventing or reversing such pathological changes,” says Fornasiero.
In addition to identifying disease-relevant proteins, understanding protein turnover and its regulation also helps to identify those proteins that are particularly susceptible to aging processes. This also opens up new avenues for future anti-aging therapies.
More information: Wenxue Li et al, Turnover atlas of proteome and phosphoproteome across mouse tissues and brain regions, Cell (2025). DOI: 10.1016/j.cell.2025.02.021
Provided by Universitätsmedizin Göttingen – Georg-August-Universität
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