Study of Salt Levels on Alpha-synuclein Aggregates May Shed New Light on Parkinson’s

Study of Salt Levels on Alpha-synuclein Aggregates May Shed New Light on Parkinson’s

Aggregation of the alpha-synuclein (α-synuclein) protein – a hallmark of Parkinson’s disease – may be influenced by salt levels within neurons, according to results of a new study. Researchers expect these findings may bring insight into the pathology of Parkinson’s disease and other protein aggregation-related diseases.

Results of the study, “Evidence For Intramolecular Antiparallel Beta-Sheet Structure In Alpha-Synuclein Fibrils From A Combination Of Two-Dimensional Infrared Spectroscopy And Atomic Force Microscopy” were published in the journal Scientific Reports.

Alpha-synuclein is an intrinsically disordered protein that is associated with the development of Parkinson’s disease by aggregating into amyloid fibrils. The formation of these structures within neurons blocks their proper activity and may lead to neuronal death. In fact, amyloid fibrils are involved in the development of nearly 50 other diseases, including Alzheimer’s disease and type 2 diabetes.

“Elucidation of the molecular details of the [α-synuclein] fibril structure is essential to understanding the mechanism of self-assembly of [α-synuclein] into fibrils, which is thought to play a role in the pathogenesis of [Parkinson’s disease],” researchers wrote.

To study the molecular conformation of these fibrils, researchers used a combination of modern laboratory techniques and showed that the presence of salt in the cells’ environment greatly influences how α-synuclein fibrils are arranged.

When salt levels are low, the molecular structure of the protein remains stabilized, but when salt is present, the protein’s conformation unfolds, exposing a region that repels water. To decrease this exposure, the unfolded protein tends to aggregate with other protein units, leading to the fibrils’ formation.

“Our finding that even small variations in [salt levels] can result in very different fibril structures could have significant physiological implications,” researchers wrote. “The high sensitivity of [α-synuclein] to the aggregation conditions might contribute to the relatively frequent occurrence of contradicting findings in this field. The mechanism proposed here should also be relevant for other amyloid forming proteins, since changes in [salt levels] are known to affect the kinetics and structure of other amyloid forming proteins as well.”

Parkinson’s disease develops when α-synuclein abnormally aggregates in neurons. In healthy neurons, this protein helps maintain the proper signaling and communication between neurons. In Parkinson’s, however, α-synuclein aggregates, which disrupts neuronal communication and leads to movement deficiencies.

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