Can Protein Shapes Indicate Parkinson's Disease?
No biomarker is currently being used in the clinic to detect Parkinson’s disease. That could all change with the discovery of a set of spinal fluid proteins that have distinct shapes for Parkinson’s patients.
Parkinson’s disease is a neurological condition that causes uncontrollable movements such as shaking. As the disease progresses, patients may have trouble walking, talking, and experience difficulty with their balance and coordination. Whilst many human diseases can be identified and diagnosed using blood or biomarkers from bodily fluids, this is not possible for Parkinson’s disease.
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Now, however, researchers from ETH Zurich are proposing that differing protein shapes could be used as a biomarker. Published in the journal Nature Structural and Molecular Biology, the research, which was led by Professor Paola Picotti, indicates 76 proteins that could be used as biomarkers for the diagnosis of Parkinson’s disease.
Although the 76 proteins were present in healthy and diseased individuals, their protein structures differed in each group. This suggested that the molecule shape indicates the presence of Parkinson’s disease, and not the protein itself. ETH Zurich’s research is the first time the analysis of protein structures in cerebrospinal fluid has been used to detect potential biomarkers for disease.
Citing that “because protein structure reflects function, we tested whether global, in situ analysis of protein structural changes provides insight into [Parkinson’s disease] pathophysiology and could inform a new concept of structural disease biomarkers,” the researchers tested the cerebrospinal fluid of 50 healthy individuals and 50 patients with the disease.
ETH Zurich’s research is the first time the analysis of protein structures in cerebrospinal fluid has been used to detect potential biomarkers for disease.
LiP-MS was then used to measure the totality of all proteins in each collected sample (proteome), identifying structural changes and the location of each exact modification. Results showed how “SF protein structural information outperformed abundance information in discriminating between healthy participants and those with [Parkinson’s disease] and improved the discriminatory performance of CSF measures of the hallmark [Parkinson’s disease] protein α-synuclein.”
The researchers concluded that analysis of the human structural proteome can guide the future development of “novel structural biomarkers of disease and enable hypothesis generation about underlying disease processes.” However, individual validation is still needed for such testing.
Marie-Therese Mackmull et al, Global, in situ analysis of the structural proteome in individuals with Parkinson's disease to identify a new class of biomarker, Nature Structural & Molecular Biology (2022). DOI: 10.1038/s41594-022-00837-0
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