Protein shapes could be a biomarker for Parkinson’s disease

Different protein structures.

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No such biomarker has been used to diagnose Parkinson’s disease. A team led by ETH Zurich Professor Paola Picotti could now help to close this gap. They identified 76 proteins that might serve as biomarkers for detecting Parkinson’s disease.

This work is unique because although the possible biomarker proteins are present in healthy and sick people, their molecules are present in the two groups in distinct shapes (or structures). The disease is not indicated by specific proteins but rather by the structure those proteins have taken. For the first time, researchers have demonstrated that it is possible to find potential markers for disease by examining the architectures of every protein present in a body fluid.

The next step will be to thoroughly test the markers found and verify them using larger groups of patients. That means these candidates are not yet available for clinical diagnoses.

Natalie de Souza, senior scientist in Paola Picotti’s group and one of the study’s co-authors, said“But from what we’ve seen so far, they’re a very strong indicator for the disease. So I’m confident that this idea of structural biomarkers will bear out.”

In this study, scientists examined the cerebrospinal fluid of 50 healthy individuals and 50 Parkinson’s patients. The study uses a technique called LiP-MS, which can identify structural changes in proteins and reveal precisely where the changes are located, to measure the proteome, or the totality of all proteins in a sample, to look for biomarkers. Conventional proteome measurements typically only capture the various protein subtypes and their quantities, not structural changes.

Since the structure of proteins is closely linked to their functions (or, indeed, dysfunctions), the researchers hypothesized that people with Parkinson’s and healthy individuals would exhibit different shapes of some proteins.

The study intends to advance the LiP-MS technique in subsequent steps to boost the biomarker signal and raise the illness detection’s sensitivity. The new biomarkers will also be tested to see how well they identify Parkinson’s disease and whether there is any overlap with other neurodegenerative illnesses like Alzheimer’s. Future research aims include identifying Parkinson’s disease subtypes and developing more precise prognoses for the disease’s progression.

Journal Reference:

  1. Mackmull MT, Nagel L, Sesterhenn F., et al. Global, in situ analysis of the structural proteome in individuals with Parkinson’s disease to identify a new class of biomarker. Nat Struct Mol Biol 29, 978–989 (2022). DOI: 10.1038/s41594-022-00837-0
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