A peptide modified by scientists may prevent the formation of toxic protein clusters in the brain, one of the causes of the tremors characteristic of Parkinson’s disease.
Man With Parkinson’s
Parkinson’s disease, the disease that the late heavyweight champ Muhammad Ali suffered from currently has no cure, and the only treatment available for it is to limit the progression of symptoms. But this could change in the coming years. In Fact, a team of researchers from the University of Bath in the UK is working on a molecule that holds promise for treating this neurodegenerative disease. Their work has been published in the Journal of Molecular Biology.
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What causes the symptoms of Parkinson’s disease?
Parkinson’s disease affects the brain in several ways. First, it causes degeneration of dopamine neurons located in the substantia nigra of the brain. This affects different neural networks. At the same time, clusters of alpha-synuclein (αS) proteins are formed in different parts of the brain. It occurs naturally in all humans, but in Parkinson’s disease, it forms so-called pathogenic clusters called Lewy bodies. These are toxic to dopamine-producing brain cells. The reduction in dopamine production causes the symptoms of Parkinson’s disease as the signals from the brain to the body start to become noisy which causes the characteristic tremor seen in people with the disease.
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A modified version of the amino acid chain
Previously, British scientists identified a library of peptides – short chains of amino acids that are the building blocks of proteins – to find the best candidate to prevent clustering. In total, they observed the effects of nearly 210 000 peptides, of which 4554W proved to be the most promising. This amino acid chain prevented aggregation of αS proteins in laboratory experiments in solutions and in living cells. In a second step, the researchers modified this peptide to optimize it. The new version of the molecule, called 4654W(N6A), was found to be significantly more effective in reducing αS aggregation and toxicity. “There is still much work to be done, but this molecule has the potential to become a drug precursor,” said study leader Jody Mason. At the moment, there are only drugs to treat the symptoms of Parkinson’s disease – we hope to be able to develop an effective drug before the onset of symptoms.”
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A better understanding of Parkinson’s disease
Other studies have been done with small molecules, but according to Richard Meade, one of the authors of the study, the small molecules did not block protein interactions. “That’s why peptides are a good solution because they are big enough to prevent protein aggregation but small enough to be used as drugs,” he says. He points out that these molecules will not only help develop treatments but will also lead to a better understanding of the disease and why proteins aggregate into toxic clusters.
Final thoughts
If this research comes to fruition and the scientists are able to develop a treatment that can prevent this debilitating disease then the lives of millions of Parkinson’s’ disease sufferers would be improved dramatically.
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