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Researchers Discover How Alpha-Synuclein May Form Toxic Aggregates

By September 27, 2023October 3rd, 2023No Comments

Researchers Discover How Alpha-Synuclein May Form Toxic Aggregates

Lipids are thought to play an important role in the aggregation of alpha-synuclein and are found in Lewy bodies, the hallmark of Parkinson’s disease. Research to date on the molecular interaction between lipids and alpha-synuclein—utilizing experimental methods such as nuclear magnetic resonance, electron paramagnetic resonance, and neutron reflectivity—has mostly been carried out at relatively low concentrations of alpha-synuclein.

Researchers at Aarhus University used vibrational sum-frequency generation (VSFG) to shed light on the role of lipid membranes in catalyzing alpha-synuclein aggregates. VSFG is a method of spectroscopy that only measures signals produced at the interface of a protein and a surface, allowing for a more precise picture in scenarios where high protein concentrations are needed, such as they are for alpha-synuclein aggregates to form.

Using this methodology, researchers discovered that alpha-synuclein undergoes a positional transformation from lying flat against the lipid surface at low concentrations to an upright position at high concentrations. “Such an upright conformation promotes lateral interactions between αS monomers and may explain how lipid membranes catalyze the formation of αS amyloids at elevated protein concentrations.”

Lead author Steven Roeters notes that VSFG may be used in the future to evaluate potential therapies for Parkinson’s. In the near term, the team at Aarhus plans to use it to evaluate how other types of surfaces, such as plastic contaminants, may influence the formation of alpha-synuclein aggregates.

Read the study

CND Life Sciences

CND Life Sciences is the creator of the Syn-One Test™, the world’s first commercially available test to visualize abnormal, phosphorylated alpha-synuclein in cutaneous nerve fibers. The test is an objective, evidence-based diagnostic tool to aid in the diagnosis of Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, pure autonomic failure, or REM sleep behavior disorder.