Vital steps towards understanding the origins of Parkinson’s disease

the origins of Parkinson's disease
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Scientists have made a crucial step towards understanding the origins of Parkinson’s disease by identifying the function of a key protein that kills the healthy brain cells of people with the neurological disorder.

Researchers, predominantly based at the Centre for Misfolding Diseases at the University of Cambridge, have discovered new evidence about a key protein, alpha-synuclein, and its role in neurons in the brain.

Lead author of the paper, Dr Giuliana Fusco, of the University of Cambridge, commented: “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.”

The research has been published in a study in Nature Communications.

New clues to understanding

Parkinson’s disease is a progressive neurological disorder, causing nerve cells in the brain to weaken or die. Its common symptoms include tremors – particularly in the hands – posture and balance difficulties, slowness, and severe stiffness in the arms and legs. Parkinson’s develops when cells in the brain stop working properly and cannot produce enough dopamine, a chemical that controls movement in the body by acting as a messenger between cells.

Parkinson’s disease is the fastest-growing neurological condition in the world, currently affecting over ten million people worldwide. It predominantly affects older people, over the age of 60, and gets more debilitating over a number of years, but early-onset Parkinson’s can affect younger people too.

The origins of Parkinson’s disease are not currently known, but scientists have theorised that it is a combination of factors such as genetics, environment, and age that cause dopamine-producing nerve cells to die.

This study has compared healthy cell conditions to those of people with Parkinson’s. All cells in the body have a plasma membrane that protects cells and typically carries nutrients in and clears toxic substances out.

Fusco, also a research Fellow at St John’s College, Cambridge, said: “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 case of alpha-synuclein 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.”

Co-author, Professor Alfonso De Simone, from Imperial College London, commented: “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.”

De Simone added: “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 affects a crucial purpose of the alpha-synuclein protein.”

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