Protein Shapes Indicate Parkinson’s Disease – ScienceDaily

Many human diseases can be detected and diagnosed using biomarkers in blood or other bodily fluids. Parkinson’s disease is different: to date, no biomarker is used in the clinic to indicate this neurodegenerative disease.

A team led by ETH Zurich professor Paola Picotto could now help close this gap. In a study just published in the journal Nature structural and molecular biologythe researchers present 76 proteins that can serve as biomarkers for the detection of Parkinson’s disease.

Different protein structure

What makes this study special is that although the potential biomarker proteins are found in both healthy and diseased individuals, their molecules are present in different forms (or structures) in each of the two groups. It is not the presence of certain proteins that indicates the disease, but the form they have taken. This is the first time scientists have shown that an analysis of the structures of all proteins in a body fluid can identify potential biomarkers for disease.

The next step will be to thoroughly test and verify the markers found with larger groups of patients. That means these candidates are not yet available for clinical diagnosis. “But from what we’ve seen so far, they’re actually a very strong indicator of the disease. So I’m very confident that this idea of ​​structural biomarkers will hold,” says Natalie de Souza, senior scientist in the group by Paola Picotti. and one of the study’s co-authors.

Measuring structural changes

In their study, the ETH Zurich researchers examined the cerebrospinal fluid of 50 healthy individuals and 50 Parkinson’s patients. The sample material was provided to them by Dutch clinicians.

To search for biomarkers, the scientists used a specific method of measuring the proteome (i.e., the totality of all proteins in a sample), called LiP-MS, which can measure structural changes in proteins and reveal exactly where the changes occurred. are located. Conventional proteome measurements tend to capture only the different types of proteins and their amounts, but not structural changes.

Because the structure of proteins is closely related to their functions (or even dysfunctions), the researchers hypothesized that people with Parkinson’s and healthy individuals will display different forms of some proteins.

The current study marks the first time the researchers have successfully applied the method to a disease.

Sharpening analysis further

In subsequent steps, the researchers want to further improve the LiP-MS method to amplify the biomarker signal and thus increase the sensitivity with which the disease can be detected. In addition, the scientists want to test the new biomarkers to assess how specifically they detect Parkinson’s disease or if there may be overlap with other neurodegenerative diseases such as Alzheimer’s disease. In the future, the researchers also want to use their method to determine subtypes of Parkinson’s disease and to make more accurate predictions about the course of the disease.

To which clinically useful diagnostics this can lead exactly is still uncertain. De Souza estimates that a future testing strategy could be based on antibodies that could differentiate between healthy and diseased protein structures. Regular use of mass spectrometers in a clinical setting is possible in principle, she says, but will be a major challenge.

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Material supplied by ETH Zurich. Originally written by Peter Rueegg. Note: Content is editable for style and length.

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