Understanding the mechanisms of chaperone proteins can be crucial for practical purposes in medicine, pharmacology, and biotechnology. It allows us to understand the changes occurring in cells that underlie neurodegenerative disorders, such as Alzheimer’s disease or Parkinson’s disease. Professor Krzysztof Liberek from the Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk has been awarded the 2023 Polish Science Foundation Award in the field of life and Earth sciences for his work on the role of chaperone proteins in repairing other faulty proteins.
“Chaperone proteins are in all cells of all organisms. These proteins ‘care for’ other proteins. They ensure that cellular proteins are in their active form so they do not denature, because denatured proteins are inactive. The research I conduct is fundamental, we are interested in basic processes occurring in the cell “, said Professor Krzysztof Liberek in an interview with Newseria Innovations, head of the Department of Protein Biochemistry.
Chaperone proteins play fundamental roles in protecting cells and entire organisms from adverse environmental conditions. Their function is to control the quality status of other proteins. When proteins do not adopt the correct spatial structure, then the chaperone proteins allow them to fold back into the correct structure. They thereby prevent the formation of protein aggregates, aggregates of proteins are incredibly important because aggregated proteins can be toxic for cells. There’s a lot of evidence suggesting that such protein aggregates occur in some neurodegenerative diseases (such as Alzheimer’s disease). Some of these aggregates can be dissolved in cells with the help of chaperone proteins.
“In neurodegenerative diseases, specific proteins aggregate. This applies to Alzheimer’s disease, Parkinson’s disease, and prion diseases. If we could somehow influence the proteins that aggregate in these diseases, we might be able to influence the course of these diseases. This is difficult, as we can do this to some extent in test tubes, but what happens in the brains of sick people is a completely different matter, so we are far from that, emphasizes the winner of the “Polish Nobel”.
In a series of five papers published between 2016 and 2021, the professor demonstrated the complexity of the process by which chaperone proteins lead to the recovery of proteins from protein aggregates and their refolding into an active spatial structure. He showed that the presence of small heat shock proteins (sHsp) during protein aggregation significantly changes the structure of aggregates, which facilitates the work of the chaperone proteins. Thanks to sHsp, chaperone proteins first remove them from the surface of the aggregate. They then initiate the unfolding of the proteins that form the aggregate and finally their release. If the process is repeated multiple times, the aggregate is completely dissolved, and a pool of active proteins is recovered.
“There are good chances that similar processes can occur in the brains of sick people. And if we could influence the chaperone proteins to act more effectively, then doctors might somehow be able to control the progression of the disease. It would, however, be necessary to diagnose this disease at a very, very early stage, when the aggregation process is not yet intense,” emphasizes Professor Krzysztof Liberek.
As neurologists emphasize, Parkinson’s disease is diagnosed at quite a late stage. On average, two years pass from the appearance of the first symptoms to the diagnosis, and in Poland, this process is even longer. Early detection of abnormalities characteristic, among others, for Parkinson’s disease or Alzheimer’s disease could be possible by determining markers in cerebrospinal fluid and blood serum. For example, Alzheimer’s disease could then be recognized at a pre-symptomatic stage, even 10-20 years before its manifestation. According to Alzheimer’s Disease International, by 2050, 131.5 million people will suffer from various types of dementia.
The Polish Science Foundation Award is often referred to as the “Polish Nobel Prize”. It is awarded to outstanding scientists for significant achievements and scientific discoveries that push the boundaries of knowledge and open up new cognitive perspectives. The prize money is PLN 200,000.
