Towards a cure for Parkinson’s disease?

THE ESSENTIAL

• The researchers specify that it will take several more years before using this molecule in a treatment.
• This research also has implications for Alzheimer’s disease and type 2 diabetes, also linked to proteins.
• More than 100,000 people have Parkinson’s disease in France.

–

Today it is impossible to cure Parkinson’s disease, the only treatments available make it possible to limit the progression of symptoms. But that could change in the years to come. A research team from the University of Bath, UK, is working on a molecule that shows promise for the cure of this neurodegenerative disease. Their work has been published in Journal of Molecular Biology.

Where do the symptoms of Parkinson’s disease come from?

Parkinson’s disease has several consequences for the brain. First, it causes degeneration of dopamine neurons, located in the substantia nigra of the brain organ. This has consequences on different neural networks. At the same time, clumps form in different areas of the brain: they are made up of alpha-synuclein (αS) protein. It is naturally present in all human beings, but in the case of Parkinson’s disease, it forms so-called pathogenic clusters, called Lewy bodies. These are toxic to dopamine-producing brain cells. This drop in dopamine production triggers the symptoms of Parkinson’s disease as the signals transmitted from the brain to the body become loud, resulting in the distinctive tremors seen in people with the condition.

A modified version of an amino acid chain

Previously, British scientists identified a library of peptides, or short chains of amino acids that are the building blocks of proteins, in order to find the best candidate to prevent the formation of clumps. In total, they observed the effects of nearly 210,000 peptides, 4554W being the most promising. This chain of amino acids prevented the aggregation of αS proteins in laboratory experiments in solutions and in living cells. Secondly, the researchers modified this peptide to optimize it. The new version of the molecule, called 4654W (N6A), was found to be significantly more effective at reducing αS aggregation and toxicity. “There is still a lot of work to do, but this molecule has the potential to be a drug precursorsaid research director Jody Mason. Today there are only drugs to treat the symptoms of Parkinson’s disease – we hope to develop an effective drug even before the symptoms develop..”

Better understand Parkinson’s disease

Other tests were done on small molecules, but according to Richard Meade, one of the study’s authors, their small size did not block protein interactions. “This is why peptides are a good option because they are large enough to prevent the protein from aggregating, but small enough to be used as medicine “, he specifies. He emphasizes that these molecules will not only participate in the development of a treatment, but they will also provide a better understanding of the disease and the reason why proteins aggregate into toxic clumps.

–