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Scientists identified the function of a mystery protein that kills brain cells in Parkinson’s disease

Parkinson’s disease is a brain disorder that produces dopamine. It’s symptoms include muscle rigidity, tremors, and changes in speech and gait. After diagnosis, treatments can help relieve symptoms, but there is no cure.

Though why people get Parkinson’s remains obscure. Still, scientists think that the disease is a combination of age, genetic and environmental factors that cause the dopamine-producing nerve cells to die, affecting the body’s ability to move.

A recent study by the scientists at St John’s College, University of Cambridge, presents compelling new evidence about what an essential protein called alpha-synuclein does in neurons in the brain.

Dr. Giuliana Fusco, Research Fellow at St John’s College, University of Cambridge, and lead author of the paper, said: “This study could unlock more information about this debilitating neurodegenerative disorder that can leave people unable to walk and talk. If we want to cure Parkinson’s, first, we need to understand the function of alpha-synuclein, a protein present in everyone’s brains. This research is a vital step towards that goal.”

“One of the top questions in Parkinson’s research is: what is the function of alpha-synuclein, the protein that under pathological conditions forms clumps that affect motor and cognitive abilities? Usually, you discover a protein for its function, and then you explore what is going wrong when disease strikes. In the alpha-synuclein case, the protein was identified for its pathological association, but we didn’t know what it did in the neuron. Our research suggests that the alpha-synuclein protein sticks like glue to the inner face of the plasma membrane of nerve cells but not to the outer- a crucial new piece of information.”

Scientists observed what was happening inside healthy conditions to pinpoint what is going wrong in the cells of people with Parkinson’s. All cells in the body have a plasma membrane that secures cells and typically moves nutrients in and gets poisonous substances out.

Using synthetic models, scientists were able to mimic brain cell membranes during the study.

From Imperial College London and one of the paper authors, Professor Alfonso De Simone, said: “When this protein is functioning normally, it plays an important part in the mechanisms by which neurons exchange signals in the brain. But it has a dark side because it malfunctions and begins to stick together in clumps, which eventually spread and kill healthy brain cells. Our research showed that this protein clings onto the inner face of the plasma membrane of brain cells, so we are slowly building a picture of this very complex disorder by studying the key function of alpha-synuclein.”

“We have thousands of proteins in our bodies, and until the function of this mystery protein is confirmed with more research, drug therapies cannot begin to be developed to tackle the origins of Parkinson’s Disease in case medication accidentally affect a crucial purpose of the alpha-synuclein protein.”

Journal Reference:

  1. Man, W.K., Tahirbegi, B., Vrettas, M.D. et al. The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition. Nat Commun 12, 927 (2021). DOI: 10.1038/s41467-021-21027-4

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