Milestone for Parkinson’s research: The amyloid protein ?-synuclein has been visualised in the cell for the first time
The protein ?-synuclein plays an important role in Parkinson’s and other neurodegenerative diseases. Although a considerable amount is known about the structure of the protein within the Parkinson’s-typical amyloid deposits, nothing was known about its original state in the healthy cell up to now. Scientists from the Leibniz-Institut für Molekulare Pharmakologie (FMP) in Berlin have now for the first time visualised the protein in healthy cells with the help of high resolution spectroscopic procedures. Surprisingly, they discovered an unstructured state. The new findings, which have appeared in Nature and Nature Communications, represent a milestone for research worldwide: It is now known that the structure of the protein changes dramatically over the course of the disease.
Neurodegenerative diseases such as Parkinson’s, Alzheimer’s or Huntington’s have one thing in common: so-called amyloid aggregates are deposited in the brain. Amyloid is the umbrella term for protein fragments that are produced by the body and that ultimately lead to the demise of nerve cells. The protein ?-synuclein is one of the main components of the amyloid aggregates and therefore plays a major role in the development of Parkinson’s disease. Much is known about the structural aspects of these aggregates. For example, it is known that ?-synuclein has a very concrete structure, which means that it is based on a blueprint that follows a specific pattern. And, in contrast to this, it is known that the isolated, purified protein has no structure whatsoever.
State of the protein ?-synuclein in living, healthy cells: The central NAC region (grey) is well protected. The protein ensures that no interaction occurs with the cytoplasm (white) and other cell components. In the case of neurodegenerative changes, the grey areas would grow together and form amyloid structures
Image: Philipp Selenko